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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): January 11, 2021

 

Heron Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

 

 

Delaware		001-33221		94-2875566
(State or other jurisdiction of incorporation)		(Commission File Number)		(I.R.S. Employer Identification No.)

 

4242 Campus Point Court, Suite 200, San Diego, CA		92121
(Address of principal executive offices)		(Zip Code)

 

Registrant’s telephone number, including area code (858) 251-4400

N/A

(Former name or former address, if changed since last report)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

 

☐	Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

☐	Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

☐	Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

☐	Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common Stock, par value $0.01 per share		HRTX		The Nasdaq Capital Market

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company  ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  ☐

 

 

 

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Item 2.02 Results of Operations and Financial Condition.

On January 11, 2021, Heron Therapeutics, Inc. (the “Company”) issued a press release announcing, among other things, certain of its financial results for the three and twelve months ended December 31, 2020 (the “Press Release”). A copy of the Press Release is furnished herewith as Exhibit 99.1.

This Item 2.02 and the Press Release attached hereto as Exhibit 99.1 are being furnished to the Securities and Exchange Commission.

 

Item 7.01 Regulation FD Disclosure.

Press Release.

On January 11, 2021, the Company issued the Press Release providing, among other things, a general update on corporate progress, as described in the Press Release.

Corporate Presentation.

A copy of presentation materials describing the business of the Company, all or a part of which may be used by the Company in investor or scientific presentations from time to time, is furnished herewith as Exhibit 99.2 (the “Corporate Presentation”). The Corporate Presentation has also been posted on the Company’s website at www.herontx.com. The Company does not undertake any obligation to update the Corporate Presentation.

This Item 7.01, the Press Release and the Corporate Presentation are being furnished to the Securities and Exchange Commission.

 

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits.

 

Exhibit No.		Description
99.1		Press Release, dated January 11, 2021
99.2		Corporate Presentation, dated January 11, 2021
104		Cover Page Interactive Data File (embedded within the Inline XBRL document)

 

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SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

			Heron Therapeutics, Inc.
Date: January 11, 2021			/s/ David Szekeres
			David Szekeres Executive Vice President, Chief Operating Officer

 

Exhibit 99.1

 

 

Heron Therapeutics Highlights Progress in Pain Management and CINV Franchises and Announces New Development Program

 

- Preliminary Full-Year 2020 Net Product Sales for CINV Franchise of Approximately $88.3 Million, versus Guidance of $85 Million -

 

- Full-Year 2021 Net Product Sales Guidance for CINV Franchise of $130 Million to $145 Million -

 

- New Drug Application for HTX-011 for Postoperative Pain Management is Under Review in the US with a May 12, 2021 PDUFA Date -

 

- Preliminary Results From Phase 1b Bunionectomy Study with HTX-034 Shows Pain Reduction Through 96 Hours with 45.5% of Patients Opioid-Free Through Day 15 -

 

- Preliminary Results from Phase 1 Study of Low Dose HTX-019 IV Injection

Demonstrated Bioequivalence to Approved Oral Aprepitant 40 mg Dose
for Prevention of Postoperative Nausea and Vomiting -

 

SAN DIEGO, Jan. 11, 2021 /PRNewswire/ -- Heron Therapeutics, Inc. (Nasdaq: HRTX), a commercial-stage biotechnology company focused on improving the lives of patients by developing best-in-class treatments to address some of the most important unmet patient needs, today highlights progress in its pain management and chemotherapy-induced nausea and vomiting (CINV) franchises and announces a new development program for postoperative nausea and vomiting (PONV).

 

Recent Corporate Progress

 

Pain Management Franchise

 

 

 

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CINV Franchise

 

 

 

 

PONV Franchise

 

 

Corporate Update

 

 

 

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“We have made important advances in 2020 in both our pain management and CINV franchises, highlighted by receiving an EU marketing authorization for ZYNRELEF^TM (also known as HTX-011), the rapid resubmission to the FDA of the NDA for HTX-011, very promising clinical data with HTX-034, and maintaining stronger than expected net product sales for CINVANTI. We are also excited to announce the development of HTX-019 for PONV, a market that is approximately 20-times larger than CINV, with an expected NDA submission late this year,” said Barry Quart, Pharm.D., Chairman and Chief Executive Officer of Heron. “2021 should be a transformational year for Heron with significant growth in our CINV products with net product sales guidance of $130 million - $145 million and the anticipated launch of HTX-011, if approved by the FDA.”

 

About HTX-011 for Postoperative Pain (ZYNRELEF in the European Union and European Economic Area)

 

HTX-011, an investigational non-opioid analgesic, is a dual-acting, fixed-dose combination of the local anesthetic bupivacaine with a low dose of the nonsteroidal anti-inflammatory drug meloxicam. It is the first and only extended-release local anesthetic to demonstrate in Phase 3 studies significantly reduced pain and opioid use through 72 hours compared to bupivacaine solution, the current standard-of-care local anesthetic for postoperative pain control. The U.S. FDA granted Breakthrough Therapy designation to HTX-011 and the NDA received Priority Review designation. A complete response letter (CRL) was received from the FDA regarding the NDA for HTX-011 in June 2020 relating to non‑clinical information. No clinical safety or efficacy issues and no chemistry, manufacturing and controls (CMC) issues were identified. Heron resubmitted an NDA to the FDA for HTX-011 in November 2020 and the FDA set a PDUFA goal date of May 12, 2021. Heron is working to respond to a list of questions received from Health Canada in July 2020. In September 2020, the European Commission (EC) granted a marketing authorization for ZYNRELEF (also known as HTX-011) for the treatment of somatic postoperative pain from small- to medium-sized surgical wounds in adults. The EC’s centralized marketing authorization is valid for the 27 countries that are members of the European Union, and the other countries in the European Economic Area, including the United Kingdom.

 

About HTX-034 for Postoperative Pain

 

HTX-034, an investigational non-opioid analgesic, is a triple-acting, fixed-dose combination of the local anesthetic bupivacaine with a low dose of the nonsteroidal anti-inflammatory drug meloxicam and aprepitant, an additional agent that further potentiates the activity of bupivacaine. HTX-034 is formulated in the same proprietary polymer as HTX-011. By combining two different mechanisms that each enhance the activity of the local anesthetic bupivacaine, HTX-034 is designed to provide superior and prolonged analgesia. Local administration of HTX-034 in a validated preclinical postoperative pain model resulted in sustained analgesia for 7 days.

 

About CINVANTI (Aprepitant) Injectable Emulsion

CINVANTI, in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin as a single-dose regimen, delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen, and nausea and vomiting

 

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associated with initial and repeat courses of MEC as a 3-day regimen. CINVANTI is an IV formulation of aprepitant, a substance P/neurokinin-1 (NK₁) receptor antagonist (RA). CINVANTI is the first IV formulation to directly deliver aprepitant, the active ingredient in EMEND^® capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK₁ RA to significantly reduce nausea and vomiting in both the acute phase (0–24 hours after chemotherapy) and the delayed phase (24–120 hours after chemotherapy). The FDA-approved dosing administration included in the United States prescribing information for CINVANTI is a 30-minute IV infusion or a 2-minute IV injection.

 

CINVANTI is under investigation for the treatment of COVID-19 as a daily 2-minute IV injection when added to the current standard of care.

Please see full prescribing information at www.CINVANTI.com.

 

About HTX-019 for Postoperative Nausea and Vomiting

HTX-019 is an IV injectable emulsion formulation designed to directly deliver aprepitant, the active ingredient in EMEND^® capsules, which is the only NK₁ RA to be approved in the United States for the prevention of PONV in adults. The FDA-approved dosing for oral EMEND is 40 mg capsules within 3 hours prior to induction of anesthesia for surgery. In a Phase 1 clinical trial, HTX-019 32 mg as a 30-second IV injection was demonstrated to be bioequivalent to oral aprepitant 40 mg.

 

About SUSTOL (Granisetron) Extended-Release Injection

 

SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. SUSTOL is an extended-release, injectable 5-HT₃ RA that utilizes Heron’s Biochronomer^® drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days. The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical studies that evaluated SUSTOL’s efficacy and safety in more than 2,000 patients with cancer. SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0–24 hours after chemotherapy) and delayed phase (24–120 hours after chemotherapy).

 

Please see full prescribing information at www.SUSTOL.com.

 

About Heron Therapeutics, Inc.

 

Heron Therapeutics, Inc. is a commercial-stage biotechnology company focused on improving the lives of patients by developing best-in-class treatments to address some of the most important unmet patient needs. Heron is developing novel, patient-focused solutions that apply its innovative science and technologies to already-approved pharmacological agents for patients suffering from pain or cancer. For more information, visit www.herontx.com.

Forward-looking Statements

This news release contains "forward-looking statements" as defined by the Private Securities Litigation Reform Act of 1995. Heron cautions readers that forward-looking statements are based on management's expectations and assumptions as of the date of this news release and

 

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are subject to certain risks and uncertainties that could cause actual results to differ materially, including, but not limited to, those associated with: adjustments to the preliminary fourth-quarter 2020 and full-year 2020 net product sales for the CINV franchise in connection with completion of financial closing procedures and an audit for the 2020 fiscal year; risks associated with the full-year 2021 net product sales guidance for the CINV franchise; whether the FDA approves the NDA for HTX-011; the timing of the commercial launch of HTX-011 in the U.S., if approved; the timing of the commercial launch of ZYNRELEF in Europe; the timing of Health Canada's NDS review process for HTX-011; whether Health Canada issues a Notice of Compliance for the NDS for HTX-011; the timing and results of studies for the HTX-034 and PONV development programs; the expected future balances of Heron’s cash, cash equivalents and short-term investments; the expected duration over which Heron’s cash, cash equivalents and short-term investments balances will fund its operations; the extent of the impact of the ongoing Coronavirus Disease 2019 (COVID-19) pandemic on our business; and other risks and uncertainties identified in the Company's filings with the U.S. Securities and Exchange Commission. Forward-looking statements reflect our analysis only on their stated date, and Heron takes no obligation to update or revise these statements except as may be required by law.

 

Investor Relations and Media Contact:

David Szekeres
EVP, Chief Operating Officer
Heron Therapeutics, Inc.

dszekeres@herontx.com

858-251-4447

 

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Heron Therapeutics Update January 11, 2021 Exhibit 99.2 1

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 involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. These risks and uncertainties include, but are not limited to, those associated with: adjustments to the preliminary fourth-quarter 2020 and full-year 2020 net product sales for the CINV franchise in connection with the completion of the financial closing procedures and an audit for the 2020 fiscal year; risks associated with achieving the full-year 2021 net product sales guidance for the CINV franchise; whether the FDA approves the NDA for HTX-011; the timing of the commercial launch of HTX-011 in the U.S.; the timing of the commercial launch of ZYNRELEF in Europe; the timing of Health Canada's NDS review process for HTX-011; whether Health Canada issues a Notice of Compliance for the NDS for HTX-011; the timing and results of studies for HTX-011, the HTX-034 development program, and the PONV development program; the expected future balances of Heron’s cash, cash equivalents and short-term investments; the expected duration over which Heron’s cash, cash equivalents and short-term investments balances will fund its operations; the extent of the impact of the ongoing Coronavirus Disease 2019 (COVID-19) pandemic on our business; and other risks and uncertainties identified in the Company's filings with the Securities and Exchange Commission. Forward-looking statements reflect our analysis only on their stated date, and we take no obligation to update or revise these statements except as may be required by law. Forward-Looking Statements

CINV PONV Pain Management Corporate Updates Strong Financial Positioning Preliminary Q4 2020 net product sales for CINV franchise of ~$20.3 Million Preliminary full-year 2020 net product sales for CINV franchise of ~$88.3 Million Versus Guidance of $85 Million Full-year 2021 net product sales guidance for CINV franchise of $130-$145 Million Preliminary 2020 year-end cash balance of ~$208.5 Million Investment Areas Clinical/Regulatory Updates HTX-011 – New Drug Application for postoperative pain management is under review in the US May 12, 2021 PDUFA Date HTX-034 – Preliminary results from Phase 1b bunionectomy study shows pain reduction through 96 hours with 45.5% of patients opioid-free through day 15 HTX-019 – Preliminary results from Phase 1 study of low dose IV injection demonstrated bioequivalence to approved oral aprepitant 40 mg dose for prevention of postoperative nausea and vomiting 3

Heron Pipeline Marketing Applications Under Review in the U.S. and Canada, and Approved in EU HTX-011 (bupivacaine/meloxicam) PAIN MANAGEMENT *CINV: Chemotherapy-induced nausea and vomiting. SUSTOL® (granisetron) extended-release injection is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. CINVANTI® (aprepitant) injectable emulsion, in combination with other antiemetic agentsis indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin as a single-dose regimen, delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen, and nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen. CINVANTI has not been studied for treatment of established nausea and vomiting. Under Investigation for Postoperative Pain via Local Application HTX-034 (bupivacaine/meloxicam/aprepitant) HTX-011, HTX-034 and HTX-019 are investigational new drugs and are not approved by the FDA SUSTOL® (granisetron) extended-release injection CINV* US FDA Approved for CINV Prevention* HTX-019 (aprepitant) injectable emulsion IND active for PONV BE Demonstrated to Oral Aprepitant PONV* Fast Track and Breakthrough Therapy designations granted by FDA US NDA: resubmitted 11/12/2020; PDUFA goal date 05/12/2021 Exposure data for excipients submitted to support reproductive toxicology studies; impurity specification lowered No issues related to clinical efficacy or safety, or manufacturing EU MAA: ZYNRELEF™ Authorized by European Commission NDA planned for 4Q2021 Preliminary 2020 net product sales for CINV franchise of ~$88.3M

Pharmacokinetic data generated for 3 excipients in toxicology animals and patients receiving HTX-011 400 mg in TKA and C-section studies Cmax of excipients at doses administered in reproductive toxicology studies are >50- to >200-fold higher than observed in patients receiving highest dose of HTX-011 Substantially higher exposures observed in toxicology species validates acceptability of submitted studies Submitted pharmacokinetic data expected to address 3 of the 4 issues in CRL Fourth CRL issue addressed by lowering impurity specification for final drug product to FDA agreed upon level FDA has acknowledged Class 2 resubmission with 6-month review clock: PDUFA goal date of 05/12/2021 NDA Resubmitted Based on Guidance at Type A Meeting

DMSO: Animal Pharmacokinetics (PK) vs Human Plasma Levels in TKA Study Animal PK NOAEL Dose Level Human PK (HTX-011 400 mg) Note: Mean Plasma Concentration Time Profiles of DMSO in Pregnant Rats and Rabbits (1,000 mg/kg/day DMSO via Oral Administration) and in Humans (HTX-011 400 mg/12 mg via Installation into the Surgical Site) DMSO Cmax in toxicology animals 106- to 129-fold higher than humans

Maleic Acid: Animal Pharmacokinetics vs Human Plasma Levels in TKA Study Note: Mean Plasma Concentration Time Profiles of Maleic Acid in Pregnant (20 mg/kg/day Maleic Acid via Oral Administration) and in Humans (HTX-011 400 mg/12 mg via Installation into the Surgical Site) Maleic Acid Cmax in toxicology animals >50-fold higher than humans Rabbit PK NOAEL Dose Level Human PK (HTX-011 400 mg)

Triacetin: Animal Pharmacokinetics vs Human Plasma Levels in TKA Study Note: Mean Plasma Concentration Time Profiles of Triacetin in Rats (1,000 mg/kg Triacetin via Oral Administration) and in Humans (HTX-011 400 mg/12 mg via Installation into the Surgical Site) Rat PK NOAEL Dose Level Human PK (HTX-011 400 mg) Triacetin Cmax in toxicology animals >200-fold higher than humans

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

Existing Platform Advantages We are prepared for the potential launch of HTX-011. Critical teams are already in place, with extensive experience in successful hospital launches. Established Platform With Experienced Teams in Place Strong KOL relationships Successful hospital and pain management launch experience IDN/hospital/ASC expertise and relationships Reimbursement infrastructure in place GPO contracts in place Full-line wholesaler agreements and 3PL in place Safety monitoring structure in place Proven compliant execution Robust systems in place and pressure tested for launch Commercial Leadership Payer Key Account Management Backbone Infrastructure Medical Science Liaisons Marketing and Sales Pharmaco-vigilance Regulatory and Compliance Trade and Distribution GPO

A Proven Track Record of Hospital Launch Success Achieved >40% Market Share From Entrenched Competitor 40.000 110.000 100.000 60.000 90.000 70.000 80.000 50.000 30.000 20.000 0 10.000 120.000 2019-Q1 2019-Q4 2019-Q2 66,983 2019-Q3 2018-Q2 2018-Q1 2018-Q3 2018-Q4 8,832 119,922 28,178 52,906 88,228 102,990 Hospital Units Hospital Share CINV Hospital Share/Units Source: IMS DDD12.25.20, 867 1.5.21 Heron launched CINVANTI in January 2018 Achieved significant market share, in a very short time period Outstanding execution: Superior pricing and contracting Providing 340B discount Differentiated product attributes Rapid formulary adoption Accelerated account pull-through Trade and reimbursement expertise We will leverage the success and experience gained from CINVANTI as we enter the postoperative pain management landscape with HTX-011.

Heron is positioned for a successful launch HTX-011 Is Well Positioned on Core Drivers to Create Fast Access and Uptake High Awareness with key formulary decision makers Outperforms both branded and generic competition on every important core attribute for a LA Reduction in Severe Pain Elimination of Opioid Discharge Prescriptions 72 Hour Duration Source: Company-sponsored ATU Study July 2020 – Survey of 386 surgeons, anesthesiologists, pharmacists, NP/Pas of potential use of an approved product with the attributes for which we are developing HTX-011 *Pharmacists were required to be involved in formulary decisions to qualify for the survey HTX-011 is an investigational new drug and not approved by the FDA HTX-011 Aided Awareness P&T Decision Makers

Importance of Core Attributes in Selecting a LA Top 2 Boxes HTX-011 Is Well Positioned on Core Drivers to Create Fast Access and Uptake Mean Product Rating on Core Attributes 1-5 Scale HTX-011 Exparel Bupivacaine On-Q 3 5 Source: Company-sponsored ATU Study July 2020 – Survey of 386 surgeons, anesthesiologists, pharmacists, NP/Pas of potential use of an approved product with the attributes for which we are developing HTX-011 HTX-011 is an investigational new drug and not approved by the FDA

Published Peer-Reviewed Manuscripts EPOCH 1 (301), Regional Anesthesia & Pain Medicine EPOCH 2 (302), Hernia Hernia Follow-on (215), Surgery EPOC TKA (209), Journal of Arthroplasty Mechanism of Action, Regional Anesthesia & Pain Medicine Truven HEOR (Opioid Naïve Users), Journal of Managed Care & Specialty Pharmacy Accepted for publication: Bunion (218), J. Am Podiatric Med Assoc (JAPMA) Truven HEOR, JMCP (Persistent Opioid Users) 38 posters and abstracts have been accepted and presented at key Congresses* Large Body of Peer-Reviewed Data for Launch *Includes congress publications from 2016-2020 based on Preclinical and Phase 2 studies (2016-2017) and Phase 3, Phase 3 Follow-On and Retrospective studies (2018-2020). 2020 congress publications include video/audio presentations at virtual congresses. HTX-011 is an investigational new drug and not approved by the FDA

In 2019 Branded Use Grew to Over $1B, however, 2020 has been Impacted by COVID 19 On-Q sales are estimated at ~$150M (down mid-single digits) / Avanos Earnings Call 11/05/19 $63M $143M $403M $472M $1,693M $612M 2019 $ 1 Billion in Branded Drug Utilization +14% On-Q Local Anesthetics  Exparel Ofirmev Opioids Source: SHA Symphony Health Drug Data FY 2019, SHA Symphony Health Drug Data through 12-25-2020 – FY data forecasted HTX-011 is an investigational new drug and not approved by the FDA

HTX-011 Competitive Position Across Settings of Care Hospital Inpatient 47% (6.6M procedures) Bundled in DRG 56% (3.7M) of inpatient procedures are done in 340B hospitals Hospital Outpatient 43% (6.0M procedures) 16% (1.0M) have Medicare reimbursement (3-year pass-through) 57% (3.4M) eligible for 340B discount Multiple SKUs – lower average costs Ambulatory Surgical Centers 9% (1.3M procedures) 17% (0.2M) eligible for Medicare reimbursement at ASP + 6% Multiple SKUs – lower average costs 14 MILLION Target Procedures 52% of the opportunity lends itself to favorable reimbursement and access Source: Heron estimate for procedure volume by site of care based on 2018 DRG Claims (data 2017) / DRG revised Claims Data 2020 (data 2017). OVERALL TOTAL HTX-011 has lower acquisition cost benefit over bundled branded products Only HTX-011 will have HOPD reimbursement – 3-year pass-through Only HTX-011 will offer 340B pricing HTX-011 is an investigational new drug and not approved by the FDA

New CMS OPPS* Rules CMS will eliminate the Inpatient Procedure Only (IPO) list over 3 years starting in CY 2021 In CY 2021 266 musculoskeletal-related procedures will be removed from (IPO) CMS will continue to package non-opioid pain management products in the hospital outpatient setting but products will remain unpackaged in ASC setting at ASP plus 6 percent. CMS indicated they will consider outpatient unbundling with real world peer reviewed evidence of opioid prescription elimination Market Dynamics are Shifting in Favor of HTX-011 and Will Accelerate Outpatient Growth *OPPS: Outpatient Perspective Payment System, HOPD: Hospital Outpatient Department HTX-011 is an investigational new drug and not approved by the FDA Source: Heron estimate for procedure volume by site of care based on 2018 DRG Claims (data 2017) / DRG revised Claims Data 2020 (data 2017).

Impact of Previous CMS Rule Change on TKA Outpatient Moved from 4% of TKA Procedures to 46% in Less Than 3 Years 98% 2% 84% 16% 74% 26% January 1, 2018 CMS removes TKA from IPO list 54% 46% Source: LexisNexis Procedure data full year 2017, 2018, 2019, 2020 data January – 12/27/20 2017 2019 2018 2020 HTX-011 is an investigational new drug and not approved by the FDA

Physicians and Pharmacists Surveyed Believe HTX-011 Will Grow the Local Anesthetics Market Product Z Alone Product Z in Combo Pre-HTX-011 With HTX-011 With the option of using Product Z available, respondents preferred using a local anesthetic 7% more of the time across their procedures Across all 4 specialty groups, respondents indicate a preference for using HTX-011 (either alone or in combination*) in ~60% of procedures. 62% 62% 61% 56% Source: Company-sponsored ATU Study July 2020 – Survey of 386 surgeons, anesthesiologists, pharmacists, NP/Pas of potential use of an approved product with the attributes for which we are developing HTX-011 * Used in combination with other local anesthetics (LA); for example, where another LA is used as a nerve block HTX-011 is an investigational new drug and not approved by the FDA

Highly Focused Launch Approach: Targeting the Top 2 Specialties – Orthopedics and General Surgeons Initial Targets Highest-volume procedures in 2 major specialties ~6.0M Orthopedic procedures ~4.5M General surgery procedures ~2.6M OB/GYN procedures ~900K Plastic surgery procedures ~14M Target Procedures Ortho and general surgeons account for 10.5M procedures or 75% of the 14M initial targets Ortho and general surgeons account for 82% of Exparel market utilization Ortho surgeons are heavy influencers (P&T, new drugs, profitability) across all settings of care Source: DRG Claims Analysis, 2016 and 2019 HTX-011 is an investigational new drug and not approved by the FDA

General Surgeons: HTX-011 Expected to Take Share from Other Treatment Options, With the Most Significant Being from Generic LAs Anticipated Local Anesthetic Use - Soft Tissue Procedures Source: Company-sponsored ATU Study July 2020 – Survey of 386 surgeons, anesthesiologists, pharmacists, NP/Pas of potential use of an approved product with the attributes for which we are developing HTX-011 HTX-011 is an investigational new drug and not approved by the FDA

Anticipated Local Anesthetic Use - Orthopedic Procedures Source: Company-sponsored ATU Study July 2020 – Survey of 386 surgeons, anesthesiologists, pharmacists, NP/Pas of potential use of an approved product with the attributes for which we are developing HTX-011 HTX-011 is an investigational new drug and not approved by the FDA Orthopedic Surgeons: HTX-011 Expected to Take Share from Other Treatment Options, With the Most Significant Being from Generic LAs

Across All Customers Surveyed, HTX-011 is Expected to Take Share from Both Exparel and Generic LAs HTX-011 Generic LA Exparel On-Q Personal Mix While generic LA usage appears to decline by 40 percentage points, 40% of HTX-011 preference includes use in combination with another local anesthetic – the majority of which will be generic LAs. % of HTX-011 Usage Alone vs. In Combo Source: Company-sponsored ATU Study July 2020 – Survey of 386 surgeons, anesthesiologists, pharmacists, NP/Pas of potential use of an approved product with the attributes for which we are developing HTX-011 HTX-011 is an investigational new drug and not approved by the FDA

Highly Focused Launch Approach: 3 Primary Hospital Targets Using $570M in Branded Pain Drugs Target 1 340B + Branded Target 2 Non-340B + Branded Target 3 Large-Procedure Volume 340B % Target Procedures Branded Utilization Hospitals Hospital Targets ASCs Targets Source: Symphony Drug Market – 2017-2019 / LexisNexis Procedure Data August 2019 YTD and DRG Claims Data 2018 HTX-011 is an investigational new drug and not approved by the FDA

Total Hospital & ASC Branded Annual WAC* $875M Targeted Hospital & ASC Branded WAC* $591M $353M Green/Yellow Branded Annual WAC* Profiled and Prioritized Fastest Moving Launch Accounts Source: Symphony Drug Market – 2017-2019 / LexisNexis Procedure Data August 2019 YTD * Excludes ON-Q 340B % Target Procedures Branded Utilization # Hospitals ASC HTX-011 is an investigational new drug and not approved by the FDA

Needle-free application Eliminates the need for up to 120 injections (as in total knee arthroplasty)1 and the time needed for aspiration and application Avoids risks of inadvertent venous punctures and eliminates accidental needle sticks with local anesthetics2 No specialized training or certification required to administer2 2 SKUs for different surgery requirements Reducing cost per procedure Minimizing waste Room temperature storage Kits fit standard OR medication carts (eg. Pyxis™) and include all components HTX-011 Ease of Use and Implementation HTX-011 is an investigational new drug and not approved by the FDA 400 mg bupivacaine 12 mg meloxicam 14-mL 200 mg bupivacaine 6 mg meloxicam 7-mL SKU: stock keeping unit. aKit components include single-dose glass vial, Luer lock syringe(s), vented vial spike, Luer lock applicator(s), and tip cap(s). Source: 1. Mont MA, Beaver WB, Dysart SH, et al. J Arthroplasty. 2018;33(1):90-96. 2. ZYNRELEF [instructions for use]. San Diego, CA: Heron Therapeutics Inc; 2020. 3. ZYNRELEF [instructions for use]. San Diego, CA: Heron Therapeutics Inc; 2020.

Market Opportunity for Zynrelef in Europe is ~15.8M Procedures of Which ~80% are Priority Procedures Notes: (1) In-scope procedures are those covered by current SmPC; (2) EU11 markets include Netherlands, Belgium, Luxembourg, Denmark, Sweden, Finland, Norway, Switzerland, Austria, Portugal, Ireland; (3) Based on 2018 procedure volumes data; Sources: National IQVIA data (2018); Regional hospital episodes data from public national statistics databases (2018); ZYNRELEF is authorized in the European Union for the treatment of somatic postoperative pain from small- to medium-sized surgical wounds in adults 15.8m in-scope procedures priority procedures (aggressively targeted) 81% 1.3M (80%) 3.3M (82%) 2.5M 2.0M (81%) 1.9M (79%) 2.7M (80%) 1.5M (80%) 4.0M 2.4M 1.6M 1.9M 3.4m 58 in-scope procedures 28 priority procedures (aggressively targeted) EU112 2.5 4.0 3.4 2.4 1.6 1.9

Resource Savings and Better Pain Management are Key Value Messages in EU5, as is Opioid Reduction, Particularly in the UK EU5 Potential alleviation of staff and bed constraints is a key value driver for Zynrelef Extended duration is a key strength to ~80% of HCPs and payers across the EU5. Demonstrating earlier discharge, reduction in length of stay and cost of care is highly compelling for payers1 ZYNRELEF’s ability to better manage severe pain versus the standard of care is a highly positive value message for HCPs Adequate treatment options for severe pain is seen as a key unmet need in Europe and for ~70% of physicians this is a key strength of ZYNRELEF Notes: 1) Aside from length of stay and cost of care, resource utilization savings can also be achieved through reducing re-admissions, less staff time and effort required to manage postoperative pain (e.g. reducing the need to adjust the titration of IV opioids every few hours, pressure on limited staff to manage pain for the entire recovery ward) and lowering total drug spend 1 2 3 Messaging around reduction in opioid use resonates highly in the UK, where there is an opioid crisis, and is an issue of growing importance in Europe In the UK, the majority of physicians feel there already is an opioid crisis and ~70% of HCPs and ~90% of payers see opioid-free as a strength of ZYNRELEF In the wider EU5, risks of opioids are perceived to be lower due to strict controls and regulations, however, there is a growing recognition due to rapidly increasing opioid consumption

There is an Opportunity in Europe to Demonstrate Significant Reductions in Hospital Length of Stay across Multiple Procedures Example: Hernia Repair (HOPE Data) Notes: 1) Open inguinal hernia repair patients were treated with ZYNRELEF and a scheduled non-opioid oral over-the-counter (OTC) analgesic regimen (N = 93). 2) Two cohorts of patients were studied under Alternating or Concurrent multimodal analgesia (MMA) regimens. Alternating regimen (N=46): OTC regimen of ibuprofen 600 mg every 6 hours (q6h) alternated 3 hours later with acetaminophen 1 g q6h. Concurrent regimen (N=47): OTC regimen of ibuprofen 600 mg and acetaminophen 1 g, taken together q6h. 3) Opioids were only prescribed at discharge for patients who rated their pain at ≥6 (NRS) or received opioid rescue medication prior to discharge. 4) Average length of stay (LOS) for 58 surgical procedures Heron is initially targeted based ZYNRELEF’s ability to address unmet needs and commercial considerations. In a survey of 304 physicians in EU5, 58 procedures were defined by wound size (small, medium and large), and classified by length of stay. The mean LOS was determined by market, specialty, and procedure. Sources: 1) Data on file. Study ZYNRELEF-304. San Diego, CA: Heron Therapeutics Inc; 2019. 2) Heron Therapeutics EU Physician Survey (2020). Zynrelef plus OTC analgesics resulted in patient discharged 2 to 3 hours after surgery with 95% of patients opioid-free through Day 151 Average length of stay for hernia repair2 There is an opportunity to demonstrate significant cost savings through stay reductions for hernia repair and other procedures Zynrelef may allow a greater number of procedures to be preformed in the outpatient setting

HTX-011 Clinical Development Postoperative Pain

EPOCH 1 (Bunionectomy) and Follow-on Study Not actual health care provider.

EPOCH 1 Follow-on: HTX-011 + OTC Acetaminophen and Ibuprofen Kept Pain in the MiId Range Through 72 Hours Time (hour) Using Numeric Rating Scale (NRS) with window worst observation carried forward (wWOCF) OTC = Over the counter analgesic regimen of ibuprofen 600 mg q6h alternating 3 hours later with acetaminophen 1000 mg q6h EPOCH 1: Reg Anesth Pain Med. 2019;44:700-706. EPOCH 1 Follow-on accepted for publication in J. Am Podiatric Med Assoc (JAPMA) Pain Intensity Score* (Mean ± SE) HTX-011 is an investigational new drug and not approved by the FDA EPOCH 1 & EPOCH 1 Follow-On Cross-Study Comparison

HTX-011 Significantly Reduced the Proportion of Patients Experiencing Severe Pain and Increased Proportion of Opioid-Free Patients p = 0.0001 p < 0.0001 % Opioid-free Through 72 Hours EPOCH 1 Follow-on N=31 EPOCH 1 (Bunionectomy) N=100 N=155 N=157 OTC = Over the counter analgesic regimen of ibuprofen 600 mg q6h alternating 3 hours later with acetaminophen 1000 mg q6h 100% of subjects opioid free through 72 hours remained opioid free through Day 28 HTX-011 is an investigational new drug and not approved by the FDA HTX-011 ≤ 60 mg + OTC 77.4%

EPOCH 2 (Herniorrhaphy) and Follow-on Study Not actual health care provider.

EPOCH 2 Follow-on: HTX-011 + OTC Acetaminophen and Ibuprofen Kept Pain in the MiId Range Through 72 Hours Time (hour) Mean Pain Intensity Score (SE) EPOCH 2: Bupivacaine HCI 75 mg (N=172) EPOCH 2: published online Hernia. doi: 10.1007/s10029-019-02023-6. EPOCH 2-Follow-on: Surgery. doi: 10.1016/j.surg.2020.06.036 HTX-011 is an investigational new drug and not approved by the FDA OTC = Over the counter analgesic regimen of ibuprofen 600 mg q6h alternating 3 hours later with acetaminophen 1000 mg q6h EPOCH 2 & EPOCH 2 Follow-On Cross-Study Comparison

HTX-011 Significantly Reduced the Proportion of Patients Experiencing Severe Pain and Increased Proportion of Opioid-Free Patients p = 0.0486 p < 0.0001 EPOCH 2 Follow-on EPOCH 2 (Herniorrhaphy) % Opioid-free Through 72 Hours N=82 N=172 N=164 N=33 40.1% OTC = Over the counter analgesic regimen of ibuprofen 600 mg q6h alternating 3 hours later with acetaminophen 1000 mg q6h 93% of subjects opioid free through 72 hours remained opioid free through Day 28 90.9% HTX-011 is an investigational new drug and not approved by the FDA HTX-011 300 mg + OTC

HOPE-1: Real World Evidence of Opioid-Free Recovery Post Inguinal Herniorrhaphy with HTX-011 + OTC Analgesics 37

HOPE-1: Near Total Opioid-Free Recovery with HTX-011 + OTC 5% N=93 in initial pilot program Presented at the American Society of Health-System Pharmacists (ASHP) Midyear 2019 Congress, December 8-12, 2019, Las Vegas, NV. 93% HTX-011 is an investigational new drug and not approved by the FDA

Study 306 Total Knee Arthroplasty (TKA) Not actual health care provider.

Study 306 TKA: HTX-011 + Generic Non-Opioid Analgesics* Kept Pain in the MiId Range Through 72 Hours With Low Opioid Consumption and Up to 26% Opioid-Free HTX-011 is an investigational new drug and not approved by the FDA LOCF for missing pain data Cohort 1 patients received oral acetaminophen 1000 mg every 8 hours (maximum 3000 mg/d) and oral celecoxib 200 mg every 12 hours for 72 hours. Mont doi: 10.1016/j.arth.2017.07.024 Cohort 4 patients received over the counter analgesic regimen of acetaminophen 1000 mg q8h and ibuprofen 600 mg q6h for 72 hours Severe Pain (≥ 7) Mild Pain (0-4)

Cross-Study Comparison of Day 1 in Study 306 and Exparel PILLAR Study (Dysart 2019) Disclaimer This is a cross-study comparison of Study 306 to the PILLAR Study of Exparel plus bupivacaine; these comparisons do not imply a clinical benefit of HTX-011 over Exparel HTX-011 is an investigational new drug and not approved by the FDA Cross-Study Comparison of 0 – 24 Hour Results in TKA Using Pillar-Based MMA and the Same Analysis1 Study 306 PILLAR Study HTX-011 + APAP + celecoxib (Cohort 1, n=51) HTX-011 + APAP + ibuprofen (Cohort 4, n=19) Exparel + Bupivacaine1 (N = 70) Bupivacaine1 (N = 69) AUC0-24 VAS Pain 2 59.8 62.1 98.5 121.6 Opioid-Free 21.6% 47.4% 17.1% 1.4% Mean Opioid Consumption MME (SD) 10.6 (9.25) 5.9 (7.95) 45.5 (35.01) 56.8 (38.26) Log-transformed Geometric Mean Opioid Consumption MME 0.54 0.01 3.5 38.5 Discharge Ready in 24 hours Based MPADSS > 9 68.6% 73.7% Not shown Not shown 1. https://doi.org/10.1016/j.arth.2018.12.026. 2. Assumes LOCF as publication does not describe any correction for opioid use

Cross-Study Comparison of 48 Hour Results From Study 306 and Exparel Pillar Study (Mont 2017) HTX-011 is an investigational new drug and not approved by the FDA Disclaimer This is a cross-study comparison of Study 306 to the PILLAR Study of Exparel plus bupivacaine; these comparisons do not imply a clinical benefit of HTX-011 over Exparel Comparison of 48 Hr Results in TKA Using Pillar-Based MMA and the Same Analysis1 Study 306 PILLAR Study HTX-011 + APAP + celecoxib (Cohort 1, n=51) HTX-011 + APAP + ibuprofen (Cohort 4, n=19) Exparel + Bupivacine1 (N = 70) Bupivacaine1 (N = 69) Mean AUC12-48 VAS Pain 145.4 125.7 180.8 209.3 Opioid-Free 11.8% 26.3% 10% 0% Mean Opioid Consumption (MME ) 19.4 ( Median=15.8) 13.0 (Median = 5.0) Not Shown Not Shown Log-transformed Geometric Mean Opioid Consumption MME 3.0 0.3 18.7 84.9 < 20 MME @ 48 hr 58.8% 73.7% 18.6% 4.4% > 20 and < 220 MME @ 48hr 41.2% 26.3% 78.6% 87% > 220 MME @ 48 hr 0 0 2.9% 8.7% DID NOT Receive a Discharge Prescription for Opioids 76.5% 68.4% Not Shown Not Shown 1. Mont doi: 10.1016/j.arth.2017.07.024

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

HTX-034 Development Next Generation Product for Postoperative Pain

Local tissue damage activates a variety of cells, which release inflammatory mediators1,2 HTX-034, an investigational non-opioid, is a fixed-dose combination, extended-release solution of the local anesthetic bupivacaine, the nonsteroidal anti-inflammatory drug meloxicam and aprepitant, an additional agent targeting the inflammatory process that further potentiates the activity of bupivacaine References: 1. Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med. 2004;140(6):441-451. 2. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2): 267-284. In Addition to Changes in pH, Inflammation From Surgery Modifies Pain Pathways and Can Produce Hyperalgesia HTX-034 is an investigational new drug and not approved by the FDA Aprepitant

Aprepitant Has Been Shown to Significantly Reduce Postoperative Pain Medications and Lower Pain After Laparoscopic Gynecological Procedures* p<0.05 *Published results from Kakuta N, et al. J Med Invest 58:246-251;2011 (n=64) p>0.05

HTX-034 Produces Complete Elimination of Pain Through 7 Days in Pig Postoperative Pain Model HTX-011 & HTX-034 are investigational new drugs and not approved by the FDA Data from multiple animal experiments using a validated postoperative pain model in pigs from Castle et al, 2013 EPJ

These cross-study comparisons confirm that addition of aprepitant in HTX-034 enhanced the activity of bupivacaine in the formulation 45.5% of patients receiving HTX-034 21.7 mg opioid-free through Day 15 without scheduled MMA Phase 2 will begin 1Q2021 HTX-034 21.7 mg Produced Greater Pain Reduction and Lower Opioid Use than HTX-011 30 mg in Study 208 or HTX-011 60 mg in Study 301 HTX-034 21.7 mg vs HTX-011 30 mg HTX-034 21.7 mg vs Matched Bupivacaine and HTX-011 60 mg Opioid Use Through 72 hrs HTX-034 21.7 mg HTX-011 30 mg HTX-011 60 mg Median MME 2.5 mg 17 mg 12.5 mg Opioid-Free 45.5% 16.7% 28.7%

HTX-034 was well tolerated with no: Clinically meaningful differences in adverse events Serious adverse events Premature discontinuations due to adverse events Local anesthetic systemic toxicity (LAST) Wound healing related adverse events HTX-034 Phase 1b Safety Summary

HTX-019 for Postoperative Nausea and Vomiting (PONV) HTX-019 is an investigational new drug for PONV and not approved by the FDA

PONV is a large market ~20x the size of CINV HTX-019 has significant potential advantages over oral aprepitant and fosaprepitant IND active, BE to oral aprepitant demonstrated and 505(b)(2) NDA for PONV prevention planned for Q4 2021 Several hundred million dollar a year potential market opportunity, taking the majority of the oral aprepitant market and use in high risk procedures PONV HTX-019 is an investigational new drug for PONV and not approved by the FDA

Aprepitant Efficacy – Large Differential in Vomiting Episodes Compared to Ondansetron* Aprepitant delayed the time to first vomiting episode compared with ondansetron. *Published results from Gan TJ, et al. Ambul Anesth. 2007; 1082-89. Figure 5. Kaplan-Meier curves for the time to first vomiting during the 48 h following surgery. The time to first vomiting was delayed by aprepitant; P 0.001 based on the log-rank test. % of patients with No Vomiting Hours post surgery Aprepitant 40 mg p.o. Aprepitant1 125 mg p.o. Ondansetron 4 mg i.v.

2020 Cochrane Meta-Analysis Concluded That Aprepitant is the Most Effective Drug for PONV* Approximately 100 fewer patients vomiting per 1000 *Weibel S, Rücker G, Eberhart LHJ, Pace NL, Hartl HM, Jordan OL, et al. Cochrane Database of Systematic Reviews. 2020

PONV Market is >20X the size of the CINV Market PONV ~53M Patients vs. ~2.5M CINV Patients Patient Population & Market Size Approximately 65M diagnostic and surgical procedures are at risk of resulting in PONV in the US More than half of these patients are at moderate to high risk of PONV ~5M 2nd Line Rescue in 2020 Source: PONV quantitative survey DRG June 2020

Target ~ 14M Surgical Procedures Where PONV is High Clinical Concern Key Surgical Types where Postoperative Emesis could be Clinically Concerning Abdominal (GI and OB) As vomiting directly involves the gastrointestinal tract, emesis can directly injure surgical sites that involve this organ system CV / CT Cranial Retching and vomiting can lead to transient increases in blood pressure which can result in damage/disruption of arterial surgical sites Intracranial pressure increases during emesis, cranial surgeries, such as craniotomy, are at elevated risk of poor outcomes due to PONV ~14M “High Clinical Concern” Procedures in 2020 (36% of all Surgical Procedures) ~39M Surgical Procedures that Could Result in PONV ~5M Clinically Concerning Cases of PONV (35% of patients undergoing these procedures may develop PONV despite prophylaxis) Source: PONV quantitative survey DRG June 2020 HCPs are more likely to take an aggressive approach managing PONV in cases where postoperative emesis could have a negative impact on the patient’s clinical outcomes

Oral Aprepitant volume is growing rapidly at premium price despite no promotion Q2’20 WAC ~ $88/capsule Acquisition cost: $43 - $64 per capsule1 ~ 1,100 current ordering accounts2 Oral Aprepitant is Already Rapidly Growing with No Promotion, Product Limitations and High Acquisition Cost HTX-019 advantages vs. Oral Aprepitant Flexible 30-second IVP vs. oral administration Onset of action – 5 minutes vs. 1 to 3 hours Heron product promotion efforts Strategic fit with HTX-011 Same commercial organization Same Hospital & ASC targets Same surgeon, anesthesiology & pharmacy targets More convenient formulations of NK-1 class are needed based on existing PONV guidelines Source: 1 Banner Health, 2 IQVIA DDD Non-Retail data Q4’20 2018 2017 2019 135K 2020 2021 2022 2023 220K 300K 302K 362K 471K 613K Oral Aprepitant – 40MG 2021-2023 Projected Totals HTX-019 is an investigational new drug for PONV and not approved by the FDA

Large market ~ 14M target surgical procedures with significant unmet need for more convenient formulations of NK-1 class drugs Potential Significant Advantages of HTX-019 30-second IV Push injection with immediate onset of action Aprepitant is the most effective therapeutic agent for emesis 505(b)(2) regulatory pathway for existing asset Existing contract manufacturers Synergies with HTX-011 commercial organization Same target accounts and target audiences Capacity & access advantages of adding a 2nd product to promote Minimal incremental investment will improve ROI HTX-019 for PONV is Ideal Strategic Fit for Heron HTX-019 is an investigational new drug for PONV and not approved by the FDA

CINV Commercial Products

CINVANTI® Cinvanti continues to have the best overall profile compared to the other available NK1 antagonists and is completely differentiated from generic fosaprepitant with the 2-min IV Push administration Generic fosaprepitant entered the market in September 2019 and let to reduced sales of CINVANTI in 2020; however, we believe the impact of the arbitrage is substantially over, with customers returning to CINVANTI beginning in 1Q2021 SUSTOL® The Aloxi arbitrage is over and Heron has implemented an innovative strategy to refresh the value of SUSTOL The ASP for SUSTOL was reset January 2021, which should allow for increased sales CINV Franchise Preliminary 2020 net product sales for CINV franchise of ~$88.3M compared to guidance of $85M, which was increased from $70M - $80M 2021 net sales guidance for CINV franchise: $130M - $145M 2020 CINV Franchise Outlook

Launch of generic Emend IV in September 2019 resulted in declining CINVANTI sales Clinic-based practices are much faster to take advantage of the arbitrage, but are expected to return to CINVANTI post-arbitrage in early 2021 SUSTOL sales continue to be low due to the Refresh Program and should rebound in 1Q2021 Heron’s CINV Portfolio Has Generated Over $340M Since Inception, CINV Franchise Sales Will Return to Growth in 2021 & Beyond Q4 2020 CINV portfolio net sales by quarter Note: SUSTOL sales from Q4 2016- Q4 2017 of $32.05M not shown in graph $11.6M $11.2M Q1 2020 $5.2M $28.0M $3.4M $42.6M $25.2M $6.4M Q3 2020 $16.4M Q1 2018 $33.2M Q2 2018 $6.1M Q3 2018 $5.4M $23.4M $17.3M Q4 2018 $19.8M $3.6M $0.3M Q1 2019 Q2 2019 $36.4M $6.26M Q3 2019  $36.7M $34.4M Q2 2020 $0.4M Q4 2019 $0.2M $22.5M $3.5M $0.1M $0.1M $28.8M $19.8M $20.3M $34.8M $25.4M $22.7M $20.0M $20.0M $31.6M CINVANTI SUSTOL

CINVANTI – Hospital Share/Units Were Down in 1Q20 Through 3Q20 Due to the Emend IV Generic Arbitrage, but Began to Rebound in 4Q 60K 110K 40K 120K 50K 0K 70K 10K 20K 30K 80K 90K 130K 100K 2020-Q4 2018-Q1 4% 2019-Q1 2018-Q2 95K 2018-Q3 2018-Q4 2019-Q2 2019-Q3 2019-Q4 2020-Q1 2020-Q3 91K 0K 2020-Q2 9K 28K 53K 67K 99K 103K 120K 113K Pack Units 88K +5% Hospital Share Hospital Units Source:867 1.5.21, : IMS DDD Q4’20 though 12.25.20 with final week projected

CINVANTI – Clinic Share/Units Declined in 1Q20 Through 3Q20 Due to the Emend IV Generic Arbitrage, but Began to Rebound in 4Q 30K 15K 0K 25K 5K 10K 85K 20K 35K 40K 45K 50K 75K 90K 60K 55K 80K 65K 70K 95K 100K 2019-Q3 2019-Q2 42K Pack Units 22K 2018-Q3 2018-Q1 2018-Q4 2019-Q1 2019-Q4 2020-Q1 71K 2020-Q2 2020-Q3 57K 90K 86K 77K 44K 52K 2020-Q4 40K 2018-Q2 95K 39K +9% Clinic Units Clinic Share Source:867 1.5.21, IMS DDD Q4’20 though 12.25.20 with final week projected

The NK1 Market Has Grown 43% Since the Launch of CINVANTI 0.4M 2017 0.3M 0.0M 0.7M 2019 1.3M 2018 0.9M 0.1M 0.1M 1.8M 1.3M 1.5M 2020 1.9M 0.9M 0.6M 0.1M +43% EMEND  CINVANTI  AKYNZEO VIAL  FOSAPREPITANT  Source: IMS DDD Q4’20 though 12.25.20 with final week projected

Financial Summary Common shares outstanding as of September 30, 2020 totaled 90.9 million. 1 Includes $11.1 million and $34.2 million of non-cash, stock-based compensation expense for the three and nine months ended September 30, 2020, respectively. 2 Based on 90.8 million and 90.7 million weighted-average common shares outstanding for the three and nine months ended September 30, 2020, respectively. Heron ended 2020 with cash, cash equivalents and short-term investments of ~$208.5 million. Summary Statement of Operations and Net Cash Used in Operations (In thousands, except per share amounts) Three Months Ended September 30, 2020 Nine Months Ended September 30, 2020 Net product sales $ 19,965 $ 68,033 Operating expenses1 78,349 234,900 Other income, net 156 1,870 Net loss1 $ (58,228) $ (164,997) Net loss per share2 $ (0.64) $ (1.82) Net cash used in operations $ (42,054) $ (132,266) Condensed Balance Sheet Data (In thousands) September 30, 2020 Cash, cash equivalents and short-term investments $ 258,146 Accounts receivable, net $ 33,654 Total assets $ 390,023 Total stockholders’ equity $ 277,147

Key Catalysts in Pain Management & CINV Franchises HTX-011, HTX-034 and HTX-019 are investigational new drugs and not approved by the FDA HTX-011 & HTX-034 for Postoperative Pain CINVANTI ® and SUSTOL® for CINV HTX-019 for PONV • CRL received 26 June 2020 • NDA resubmitted; PDUFA goal date of 05/12/2021 • EU Centralised Procedure • European Commission Authorization received • UK Authorization received • Canadian NDS • Responses to questions in process 2020 net product sales of ~$88.3M compared to guidance of $85M for CINV franchise (raised from $70M - $80M) Bioequivalence of HTX-019 32 mg to oral aprepitant 40 mg achieved in Phase 1 study • 5050(b)(2) NDA for PONV planned for 4Q2021 • Promising HTX-034 Phase 1b bunionectomy results • Phase 2 will start 1Q 2021 net sales guidance for CINV franchise: $130M - $145M Potential approval in 2H2022