Aprepitant

HELSINKI, May 30, 2024 /PRNewswire/ -- Manufacturing of GMP material in Project Nanoenzalutamide commenced. EU/US pivotal studies are planned to start in 4Q24, with the read-out in 1Q25. One or several license/commercial supply agreements are expected to be signed during 2H24. Fimea's two-day inspection of our new GMP QC laboratory and new GMP lines is set for June 11-12. Takeda presented results from their nanoformed Biologics PoC study at DDF in Berlin, a strategic partnership was announced with CBC of Japan, a Business Finland grant of EUR 4m was won and EUR 15m was raised in a new share issue to build GMP capability to produce solid oral dosage forms for clinical trials and to create up to a dozen new product kernels like nanoenzalutamide and nanoapalutamide to be licensed out in the coming years. The previously communicated business targets for 2024: "Increased number of non-GMP and GMP projects in 2024 vs 2023" and "Improved operating free cash flow in 2024 vs 2023" are reiterated. 1-3/2024 key financials Revenue came in at EUR 0.6 million, stemming from 22 different customer projects (EUR 0.7m, 24 projects in 1-3/2023). The number of employees increased to 166 (152). Total operating costs* grew by 25 % to EUR 6.5 million (EUR 5.2 million) due to options related non-cash costs, investments in spare parts & building an internal maintenance function in addition to costs from the nanoenzalutamide project. EBITDA came in at EUR -5.7 million (EUR -4.5 million). The operating loss was EUR -6.5 million (EUR -5.1 million). The operating free cash flow improved to EUR -6.0 million (EUR -6.2 million) Basic EPS was EUR -0.09 (EUR -0.06) Cash position was EUR 41.3 million on March 31, 2024 (EUR 63.0 million).* (Numbers in Brackets Refer to the Corresponding Last Year Reporting Period, Unless Otherwise Mentioned.) * Defined as materials & services expenses, employee benefit expenses, and other operating expenses. ** Including Treasury bills. Part of the cash has been invested in short-term government bonds. ***Cash position after the new share issue was EUR 54.7 m on April 30, 2024. CEO's review "Nanoform progresses on many fronts. Since our last report we have entered Japan by making a strategic partnership with CBC, Takeda presented results from their nanoformed biologics PoC study at DDF in Berlin, we won a Business Finland grant of EUR 4m to research and develop nanoparticle-enabled formulation platforms for oral, inhaled, long-acting injectable, and high-concentration subcutaneous injectable drug delivery and we raised EUR 15m in a new share issue to build GMP capability to produce solid oral dosage forms for clinical trials and to create up to a dozen new product kernels like nanoenzalutamide and nanoapalutamide to be licensed out in the coming years. Last, but certainly not least, in project Nanoenzalutamide, we have now started clinical manufacture related to the upcoming pivotal EU/US studies. The clinical trials are expected to commence in 4Q24 and the results are expected in 1Q25. We expect nanoenzalutamide to be the first nanoformed medicine to reach the market - with a planned launch in 2027/28 in the US/EU - and to be a revenue driver for Nanoform already in the upcoming years. We expect to execute one or several licensing/commercial supply agreements in 2024 and expect these to include customary payments already at signing and later when meeting developmental- and regulatory milestones. Long-term we expect to receive royalty payments based on sales when the product is on the market. Nanoenzalutamide is expected to progress via the ANDA*/Hybrid generic pathway and as such will need to show bioequivalence versus the originator product, Xtandi®. In the eyes of the regulators, bioequivalence typically means 80% - 125% of the Cmax and AUC in a large cohort study in fed and fasted states with a 90% confidence interval." *ANDA=Abbreviated New Drug Application "The global annual sales of Xtandi® is presently USD 6bn and growing. We plan for nanoenzalutamide to take a meaningful share of this market through its highly patient centric product differentiation (1 tablet vs 4 tablets) and unique IP position (different technology, crystalline product, different excipients), while not forgetting its green attributes. We now actively pursue commercial licensing and marketing partners for the product together with our partners in the ONConcept® consortium. We see the program to be attractive to value added medicine companies as a uniquely differentiated and high value supergeneric product that can enable a product launch before market entry by other generic products based on the ASD formulation, for which the originator currently holds patents in both Europe and the US (with expiry dates in 2033). For the originator company we believe the nanocrystalline single tablet product offers a patient centric life cycle extension opportunity with compelling sustainability advantages that would be difficult for generic competitors to match. Avoiding the inherent stability challenges associated with amorphous materials is also a clear benefit for any company considering alternative formulation approaches. Xtandi-tablets are formulated using a solubility-enhancement spray-drying process to create an amorphous solid dispersion. The major challenge with spray drying is that the process often requires large amounts of undesirable and toxic organic hydrocarbon solvents. Nanoform's CESS® process uses CO2 of recycled origin, and is organic hydrocarbon solvent-free, offering a greener alternative to medicine developers that seek to be both patient- and planet-centric. Nanoform continuously improves the CESS® technology, e.g. by planning to further recycle the CO2 used by the process to become a carbon sink. This is an attractive proposition for the pharma industry to achieve its ambitious net zero goals. There are already concerns in the industry that industrial approaches with a heavy carbon footprint, e.g. spray drying, may lose their relevance in the future because of their environmental burden. The timelines for the commercial launch of nanoenzalutamide are demanding, but achievable. In 2024 we need to manufacture nanoformed GMP material for the registration batches and the pivotal bioequivalence studies. When positive, the submissions of the dossiers should be in 2025-26, with the aimed product launch after the expiry of the enzalutamide substance patent in the respective territories. For the United States this patent expiry is expected in 2027, and in Europe in 2028. We now have an inspection date from Fimea. They will do a two-day inspection of our new GMP QC laboratory and our new GMP lines 2&3 on June 11-12. A successful inspection will expand our GMP capacity by more than 3x and will help our gross margin to return to the targeted 90%+. On the business development side we have made solid progress among large pharma, with a growing interest also in our biologics technology. The US biotech sector shows clear signs of increased activity levels. While our revenue development during the last year was unsatisfactory, I am confident - based on the clearly increased - by number and depth - discussions with large-, mid-sized pharma and biotech companies, that we will reach our 2024 targets of more projects signed and improved cash flow in 2024 compared with 2023. For Nanoform the last three years has been about making large investments and building a capable organization. The coming three will be about preparing to launch nanoformed products together with partners onto the global markets. We are ready for the challenge. I look forward with confidence and excitement to the coming years. None of this can be done without our amazing employees and great partners. My sincere THANK YOU to you all for your continued dedication to Nanoform and for the inspiring and innovative work for which we're known." Best Regards, Prof. Edward Hæggström, CEO Nanoform Project Nanoenzalutamide and ASDs (amorphous solid dispersions) Nanoenzalutamide is a great opportunity for us to show that small is a powerful ingredient in formulation. Due to the inherent poor solubility of the API, the current formulation of this blockbuster medicine - for treatment of prostate cancer - has been an amorphous solid dispersion ("ASD"). Amorphous API materials are notoriously unstable, and therefore require high amounts of polymers to stabilize the API - leading to a low drug load in the product and therefore, in the case of oral solid products, often to a high number of large tablets that need to be taken by the patient. This is a known problem, in particular for patient populations with challenges to swallow. The nanocrystalline formulation developed by Nanoform offers an attractive alternative with a substantially higher drug load in the final drug product and consequently a reduced tablet burden for the patient. We are encouraged by the broad interest shown in this patient centric reformulation and we look forward to signing license/supply agreements around this product opportunity in 2024. In addition to the patient benefit, we can with our proprietary technology offer opportunities to extend IP protection for the reformulated and improved product, expecting that in many cases our innovative formulations will be patentable. Importantly, current ASD based medicines are often protected by secondary patents that claim aspects of the ASD formulation. These secondary patents, such as in the case of the product in Project Nanoenzalutamide, often extend by several years the expiration of the primary patent claiming the API. In the case of Project Nanoenzalutamide, we believe that our nanocrystalline formulation is not in the scope of the patents claiming the ASD formulation. This should potentially enable entry earlier into the market, in the jurisdictions where the ASD formulation patents remain active, compared to ASD based generic formulations. ASDs remain a leading formulation strategy for poorly soluble APIs, particularly for oral solid dosage forms. There are currently some 50 marketed medicines that are ASDs and these sell in aggregate for some USD 50bn annually in the world. We are currently looking at several other marketed ASD opportunities to replicate our early successes with Project Nanoenzalutamide in addition to those ASDs still in the global drug development pipeline. According to STARMAP®, almost 80 per cent of the 46 ASDs we so far have starmapped may be well suited to be nanoformed by CESS®. Nanoform's Q1 2024 report can be found at: Nanoform online presentation and conference call May 30, 2024, at 3:00 p.m. Helsinki time / 2:00 p.m. Stockholm time Nanoform will publish its Q1 2024 report on May 30, 2024, at 8.10 a.m. Finnish time / 7.10 a.m. Swedish time. The company will hold an online presentation and conference call the same day at 3.00 p.m. Finnish time / 2.00 p.m. Swedish time. Nanoform will be represented by CEO Edward Hæggström, CFO Albert Hæggström and CCO Christian Jones. The presentation will be delivered in English. The presentation will be broadcast live as a webcast available at: Teleconference dial-in numbers: Dial-in number to the teleconference will be received by registering via the link below. After the registration you will be provided phone numbers and a conference ID to access the conference. Questions can be presented by this dial-in function. Significant events during 1-3/2024 On January 5, 2024, Nanoform announced it had completed the First Subject First Visit (FSFV) in a trial to evaluate the relative bioavailability of its nanocrystalline enabled alternative to an amorphous solid dispersion (ASD); formulation of nanoenzalutamide and Xtandi®[1], the number one prescribed androgen receptor inhibitor first approved by the FDA in 2012 to treat prostate cancer. The single-dose, randomized, comparative bioavailability study, performed by a contract research organization in North America, compared enzalutamide 160 mg film-coated tablets (Bluepharma Farmaceutica S.A.) and Xtandi 4x40 mg film-coated tablets (Astellas Pharma Europe B.V.). On January 10, 2024, The Board of Directors of Nanoform Finland Plc decided on the issue of stock options under an option program open to all employees. The total number of option rights to be issued is at most 1,240,412. The stock options are entitled to subscribe for at most 1,240,412 shares in Nanoform. Each stock option entitles to subscribe for one new share. The subscription price for shares subscribed with stock options is EUR 1.70 per share. The total subscription price of the shares shall be paid to the company's fund for invested own free equity. On January 26, 2024, Nanoform announced that one of its leading nanoformulation drug products had received promising clinical results. These were from a relative bioavailability study of nanocrystalline-enabled enzalutamide (nanoenzalutamide) tablet formulation, an alternative to the amorphous solid dispersion (ASD) used in Xtandi®[1], the number one prescribed androgen receptor inhibitor[2] first approved by the FDA in 2012, and by the EMA in 2013 to treat prostate cancer. The nanoenzalutamide tablet formulation was developed in a partnership with the ONConcept® Consortium (Bluepharma, Helm, and Welding) whereby Nanoform´s proprietary controlled expansion of supercritical solutions (CESS®) technology provides the opportunity for an improved and differentiated finished product. Tablet-burden and dysphagia are well-documented challenges for prostate cancer patients, and the development of a 160mg, single tablet per day regimen may be preferable for patients in need of reducing their total number of daily pills. A patent application for the nanoenzalutamide formulation has already been jointly filed by Helm and Nanoform. We aim for product launch after the expiry of the enzalutamide substance patent in the respective territories. For the United States this patent expiry is expected in 2027, and in Europe in 2028. This unique IP position may allow the nanoenzalutamide product to enter the market prior to other generic competition based on the ASD formulation, which is currently patent protected in the US and Europe until 2033. [1] Xtandi is a registered trademark of Astellas Pharma Inc. [2] Source: xtandi.com On February 15, 2024, Nanoform announced that it has won a grant of up to 4.3 million euros from Business Finland, the Finnish government organization for innovation funding and trade. The grant represents 50% of the costs associated with Nanoform's research and development project for nanoparticle-enabled formulation platforms for oral, inhaled, long-acting injectable, and high-concentration subcutaneous injectable drug delivery technologies for next generation medicines. The work is expected to take place during 2024 and 2025. On February 29, 2024, Nanoform announced it had received positive results from its own pre-clinical, in vivo study of a nanocrystalline-enabled apalutamide oral formulation, which shows potential to enable a much smaller tablet than Erleada®[3], a nonsteroidal antiandrogen (NSAA) blockbuster amorphous solid dispersion (ASD) medicine used to treat prostate cancer. [3] Erleada is a registered trademark for Apalutamide owned by Johnson & Johnson / Janssen Biotech, Inc. On March 12, 2024, The Board of Directors approved share subscriptions based on stock option programs 2/2019 and 1/2020. A total of 11,200 Nanoform Finland Plc new shares were subscribed and the entire subscription price for subscriptions made with the stock options of EUR 13 thousand was entered in the Company's reserve for invested unrestricted equity. On March 26, 2024, The Board of Directors of Nanoform Finland Plc decided on the issue of stock options to key individuals. The total number of option rights to be issued is at most 200,000. The stock options entitle to subscribe for at most 200,000 shares in Nanoform. Each stock option entitles to subscribe for one new share. The subscription price for shares subscribed with stock options is EUR 3.00 per share, which is approximately 25 percent more than the closing price on 25 March 2024. The total subscription price of the shares shall be paid to the company's fund for invested own free equity. Significant events after 1-3/2024 On April 8, 2024, Nanoform announced that effective April 10, 2024, onwards, the Certified Adviser to Nanoform Finland Plc is Carnegie Investment Bank Ab (publ). The Certified Adviser to Nanoform Finland Plc until April 9, 2024, was Danske Bank A/S, Finland Branch. On April 9, 2024, Nanoform announced a collaboration with PlusVitech, a biotechnology company developing treatments for cancer, to use Nanoform's state-of-the-art nanomedicine technology to repurpose the anti-nausea medicine aprepitant as a treatment for lung cancer. The development program will include nanoforming the current active ingredient into crystalline nanoparticles and formulating a simplified dose regimen with fewer and smaller pills. The partnership is expected to include API supply for late-stage clinical programs and eventual product launch. Following PlusVitech's positive first time in human studies, a Phase 2 study with 24 patients has commenced, investigating the efficacy of high dose aprepitant in a non-small cell lung cancer (NSCLC) population that is refractory to standard treatment. The current formulation carries a high pill burden of potentially dozens of capsules per day, with a complicated regimen for patients that are most often frail and have trouble swallowing (dysphagia). The new formulation by Nanoform is designed to deliver substantially higher drug load with better bioavailability, which simplifies the dose regimen and improves patient convenience and compliance. Repurposing an existing drug offers a potentially faster, risk-reduced and cost-effective development path to provide new treatments for high medical need indications like NSCLC. On April 11, 2024, Nanoform announced a strategic partnership whereby CBC Co., Ltd. ("CBC"), will utilize its extensive experience in the Japanese pharmaceutical industry to identify opportunities for Nanoform's cutting-edge nanomedicine engineering technologies. The partnership commenced immediately, and the companies have planned several joint activities to introduce their collaboration, including the held representation of Nanoform by CBC at CPHI Japan, which took place at Tokyo Big Sight, Tokyo, from April 17-19, 2024. Nanoform's Annual General Meeting (the "AGM") was held on April 16, 2024. 46 shareholders representing more than 60 per cent of all outstanding shares and votes were represented at the meeting. The Annual General Meeting supported all the Board of Directors' proposals. The AGM approved the financial statements and discharged the Board of Directors and the CEO of the Company from liability for the financial year 2023. The AGM further resolved the number of members of the Board of Directors to be four and the AGM re-elected Miguel Calado (Chairperson), Mads Laustsen, Albert Hæggström and Jeanne Thoma as ordinary members of the Board of Directors for the next term of office. On April 24, 2024, Nanoform announced that it had successfully completed a new share issue raising EUR 15.4m by issuing 7m new shares (8.9% dilution) at EUR 2.20 (SEK 25.60) per share in order to invest in the commercialization of nanoparticle enabled formulations for next generation medicines. The placing attracted a considerable number of leading Nordic and institutional investors. The proceeds will be used to build a GMP level formulation facility to produce solid oral dosage forms for clinical trials, to development of up to a dozen pre-clinical nanocrystalline alternatives to ASD medicines ready for partnering in clinical trials and to co-fund several projects to be taken by Nanoform and its partners into clinical trials in the EU and the US, and ultimately through to the market. The total number of issued shares in the company after the placing will be 85,445,164. On May 22, 2024, at the 15th Global Drug Delivery & Formulation Summit in Berlin, Andreas Liebminger, Ph.D., Global Head of Plasma-derived Therapies Pharmaceutical Sciences, Takeda, presented data obtained in a proof of concept study, conducted in collaboration with Nanoform. Controlling the viscosity and aggregation of protein-based solutions is important for pharmaceutical formulators. Because injection volume is limited by the device, therapeutic protein formulations which are to be delivered via intramuscular or intravenous injection need to be highly concentrated. At protein concentrations greater than 200 mg*mL-1 however, viscosity increases to significantly higher than 20 cP (centipoise) to quickly exceed the maximum 40 cP viscosity deemed acceptable for a conventional subcutaneous injection. The data support the potential of Nanoform's patented biologics platform to achieve high protein concentrations in suspension formulations that are suitable for subcutaneous injection, as shown by results of syringeability and injectability studies. Company near-term business targets for 2024 Increased number of non-GMP and GMP projects signed in 2024 vs 2023 Improved operating free cash flow in 2024 vs 2023 To sign one or several license/commercial supply agreements during 2024 Company mid-term business targets 2025 To nanoform at least 70 new Active Pharmaceutical Ingredients (API) annually To have in place 35 operating production lines of which 7 to 14 are expected to be GMP production lines Over 90 percent gross margin To have 200–250 employees To be cash flow positive For further information, please contact: Albert Hæggström, CFO [email protected] / +358 29 370 0150 For investor relations queries, please contact : Henri von Haartman, Director of Investor Relations [email protected] / +46 7686 650 11 About Nanoform Nanoform is the medicine performance-enhancing company that leverages best-in-class innovative nanoparticle engineering technologies, expert formulation, and scalable GMP nano-API manufacturing to enable superior medicines for patients. The company focuses on reducing clinical attrition and on enhancing drug molecules' performance through its nanoforming technologies and formulation services, from pre-clinical to commercial scale. Nanoform will help improve bioavailability and drug delivery profiles, drive differentiation, patient adherence and extend the lifecycle potential of products. Nanoform's shares are listed on the Premier-segment of Nasdaq First North Growth Market in Helsinki (ticker: NANOFH) and Stockholm (ticker: NANOFS). Certified Adviser: Danske Bank A/S, Finland Branch, +358 40 744 1900. For more information, please visit . Forward-Looking Statements This press release contains forward-looking statements, including, without limitation, statements regarding Nanoform's strategy, business plans and focus. The words "may", "will", "could", "would", "should", "expect", "plan", "anticipate", "intend", believe", "estimate", "predict", "project", "potential", "continue", "target" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, any related to Nanoform's business, operations, clinical trials, supply chain, strategy, goals and anticipated timelines, competition from other companies, and other risks described in the Report of the Board of Directors and Financial Statements for the year ended December 31, 2023 as well as our other past disclosures. Nanoform cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. Nanoform disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent Nanoform's views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. This information was brought to you by Cision The following files are available for download: SOURCE Nanoform

Net Product Sales of $34.7 million, which increased from $29.6 million for the same period in 2023. Net Loss Per Share $(0.02), which decreased from $(0.27) for the same period in 2023. Launched partnership with CrossLink Life Sciences, LLC to expand ZYNRELEF® promotional efforts in the first quarter of 2024. Gross Margin improved to 76% for the quarter, up from 43% for the same period last year. FDA approval of expanded indication for ZYNRELEF received on January 23, 2024. Heron to host its first ever Investor Day event on Wednesday, May 15, 2024 in New York, New York. SAN DIEGO, May 7, 2024 /PRNewswire/ -- Heron Therapeutics, Inc. (Nasdaq: HRTX) ("Heron" or the "Company"), a commercial-stage biotechnology company, today announced financial results for the three months ended March 31, 2024 and highlighted recent corporate updates. "We are extremely pleased with our ability to improve the financial efficiency of the business by growing revenues, improving margins, and reducing expenses. We made tremendous progress this quarter by promptly training CrossLink sales representatives and integrating them into our commercial execution, while also training our own commercial team on the newly expanded label for ZYNRELEF," said Craig Collard, Chief Executive Officer of Heron. Business Highlights The ZYNRELEF Vial Access Needle ("VAN") program, to allow for the rapid preparation and administration of ZYNRELEF in the operating room, remains on track for a Prior Approval Supplement ("PAS") submission in Q2 2024 and an anticipated launch in late 2024. The ZYNRELEF Prefilled Syringe ("PFS"), to allow for immediate use of ZYNRELEF, continues to progress with an expected submission for approval in 2026. The training and integration of CrossLink Life Sciences, LLC ("CrossLink") sales representatives to promote ZYNRELEF to orthopedic surgeons has progressed quickly, with a total of 191 CrossLink sales representatives, to date, having completed training and actively engaging with their respective physicians. As we continue to expand our reach across the nation, we anticipate an additional fifty CrossLink sales representatives will complete training and be ready to engage with their respective physicians on ZYNRELEF within the next thirty days. Following the FDA's approval for the expanded indication of ZYNRELEF on January 23, 2024, ZYNRELEF is now approved for postsurgical analgesia for up to 72 hours after soft tissue and orthopedic surgical procedures including foot and ankle, and other procedures in which direct exposure to articular cartilage is avoided. ZYNRELEF was previously approved for foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures in adults. Heron will host its Investor Day event on Wednesday, May 15, 2024, from 9:30 a.m. – 12:30 p.m. ET in New York, New York. Members of Heron's leadership team will give presentations during the event highlighting Heron's recent organizational transformation and the commercial opportunity across the acute care and oncology franchises. To register for the event to attend in-person or virtually, please click here. Financial Guidance for 2024 The Company reaffirms its full-year 2024 guidance for Product Revenues, Net, Adjusted Operating Expenses and Adjusted EBITDA: Acute Care Franchise Acute Care Franchise Net Product Sales: For the three months ended March 31, 2024, acute care franchise Net Product Sales were $5.5 million, which increased from $3.8 million for the same period in 2023. ZYNRELEF Net Product Sales: Net Product Sales of ZYNRELEF (bupivacaine and meloxicam) extended-release solution for the three months ended March 31, 2024 was $5.0 million, which increased from $3.5 million for the same period in 2023. APONVIE® Net Product Sales: Net Product Sales of APONVIE for the three months ended March 31, 2024 was $0.5 million, which increased from $0.3M, for the same period in 2023. Oncology Care Franchise Oncology Care Franchise Net Product Sales: For the three months ended March 31, 2024, oncology care franchise Net Product Sales was $29.2 million, which increased from $25.8 million for the same period in 2023. CINVANTI® Net Product Sales: Net Product Sales of CINVANTI (aprepitant) injectable emulsion for the three months ended March 31, 2024 was $25.6 million, which increased from $22.8 million for the same period in 2023. SUSTOL® Net Product Sales: Net Product Sales of SUSTOL (granisetron) extended-release injection for the three months ended March 31, 2024 was $3.6 million, which increased from $3.0 million, for the same period in 2023. Conference Call and Webcast Heron will host a conference call and webcast on May 7, 2024 at 8:30 a.m. ET. The conference call can be accessed by dialing (646) 307-1963 for domestic callers and (800) 715-9871 for international callers. Please provide the operator with the passcode 1497932 to join the conference call. The conference call will also be available via webcast under the Investor Relations section of Heron's website at . An archive of the teleconference and webcast will also be made available on Heron's website for sixty days following the call. About ZYNRELEF for Postoperative Pain ZYNRELEF is the first and only dual-acting local anesthetic that delivers a fixed-dose combination of the local anesthetic bupivacaine and a low dose of nonsteroidal anti-inflammatory drug meloxicam. ZYNRELEF is the first and only extended-release local anesthetic to demonstrate in Phase 3 studies significantly reduced pain and significantly increased proportion of patients requiring no opioids through the first 72 hours following surgery compared to bupivacaine solution, the current standard-of-care local anesthetic for postoperative pain control. ZYNRELEF was initially approved by the U.S. Food and Drug Administration (the "FDA") in May 2021 for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty. In December 2021, the FDA approved an expansion of ZYNRELEF's indication to include foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures. On January 23, 2024, the FDA approved ZYNRELEF for soft tissue and orthopedic surgical procedures including foot and ankle, and other procedures in which direct exposure to articular cartilage is avoided. Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures. Please see full prescribing information, including Boxed Warning, at . About APONVIE for Postoperative Nausea and Vomiting (PONV) APONVIE is a substance NK1 Receptor Antagonist (RA), indicated for the prevention of PONV in adults. Delivered via a 30-second IV push, APONVIE 32 mg was demonstrated to be bioequivalent to oral aprepitant 40 mg with rapid achievement of therapeutic drug levels. APONVIE is the same formulation as Heron's approved drug product CINVANTI. APONVIE is supplied in a single-dose vial that delivers the full 32 mg dose for PONV. APONVIE was approved by the FDA in September 2022 and became commercially available in the U.S. on March 6, 2023. Please see full prescribing information at . About CINVANTI for Chemotherapy Induced Nausea and Vomiting (CINV) Prevention 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 associated with initial and repeat courses of MEC as a 3-day regimen. CINVANTI is an IV formulation of aprepitant, an NK1 RA. CINVANTI is the first IV formulation to directly deliver aprepitant, the active ingredient in EMEND® capsules. Aprepitant (including its prodrug, fosaprepitant) is a 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 U.S. prescribing information for CINVANTI include 100 mg or 130 mg administered as a 30-minute IV infusion or a 2-minute IV injection. Please see full prescribing information at . About SUSTOL for CINV Prevention 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-hydroxytryptamine type 3 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 . About Heron Therapeutics, Inc. Heron Therapeutics, Inc. is a commercial-stage biotechnology company focused on improving the lives of patients by developing and commercializing therapeutic innovations that improve medical care. Our advanced science, patented technologies, and innovative approach to drug discovery and development have allowed us to create and commercialize a portfolio of products that aim to advance the standard-of-care for acute care and oncology patients. For more information, visit . Non-GAAP Financial Measures To supplement our financial results presented on a GAAP basis, we have included information about certain non-GAAP financial measures. We believe the presentation of these non-GAAP financial measures, when viewed with our results under GAAP, provide analysts, investors, lenders, and other third parties with insights into how we evaluate normal operational activities, including our ability to generate cash from operations, on a comparable year-over-year basis and manage our budgeting and forecasting. In our quarterly and annual reports, earnings press releases and conference calls, we may discuss the following financial measures that are not calculated in accordance with GAAP, to supplement our consolidated financial statements presented on a GAAP basis. Adjusted EBITDA Adjusted EBITDA is a non-GAAP financial measure that represents GAAP net income or loss adjusted to exclude interest expense, interest income, the benefit from or provision for income taxes, depreciation, amortization, stock-based compensation, and other adjustments to reflect changes that occur in our business but do not represent ongoing operations. Adjusted EBITDA, as used by us, may be calculated differently from, and therefore may not be comparable to, similarly titled measures used by other companies. There are several limitations related to the use of adjusted EBITDA rather than net income or loss, which is the nearest GAAP equivalent, such as: adjusted EBITDA excludes depreciation and amortization, and, although these are non-cash expenses, the assets being depreciated or amortized may have to be replaced in the future, the cash requirements for which are not reflected in adjusted EBITDA; we exclude stock-based compensation expense from adjusted EBITDA although: (i) it has been, and will continue to be for the foreseeable future, a significant recurring expense for our business and an important part of our compensation strategy; and (ii) if we did not pay out a portion of our compensation in the form of stock-based compensation, the cash salary expense included in operating expenses would be higher, which would affect our cash position; adjusted EBITDA does not reflect changes in, or cash requirements for, working capital needs; adjusted EBITDA does not reflect the benefit from or provision for income taxes or the cash requirements to pay taxes; adjusted EBITDA does not reflect historical cash expenditures or future requirements for capital expenditures or contractual commitments; we exclude restructuring expenses from adjusted EBITDA. Restructuring expenses primarily include employee severance and contract termination costs that are not related to acquisitions. The amount and/or frequency of these restructuring expenses are not part of our underlying business; Adjusted Operating Expenses Adjusted operating expenses is a non-GAAP financial measure that represents GAAP operating expenses adjusted to exclude stock-based compensation expense, depreciation and amortization, and other adjustments to reflect changes that occur in our business but do not represent ongoing operations. The Company has not provided a reconciliation of its full-year 2024 guidance for adjusted EBITDA or adjusted operating expenses to the most directly comparable forward-looking GAAP measures, in reliance on the unreasonable efforts exception provided under Item 10(e)(1)(i)(B) of Regulation S-K, because the Company is unable to predict, without unreasonable efforts, the timing and amount of items that would be included in such a reconciliation, including, but not limited to, stock-based compensation expense, acquisition related expense and litigation settlements. These items are uncertain and depend on various factors that are outside of the Company's control or cannot be reasonably predicted. While the Company is unable to address the probable significance of these items, they could have a material impact on GAAP net income and operating expenses for the guidance period. 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 are subject to certain risks and uncertainties that could cause actual results to differ materially. Therefore, you should not place undue reliance on forward-looking statements. Examples of forward-looking statements include, among others, statements we make regarding the potential market opportunities for ZYNRELEF, APONVIE, CINVANTI and SUSTOL; revenue, adjusted EBITDA and other financial guidance provided by the Company; the results of the commercial launch of APONVIE; the potential additional market opportunity for the expanded U.S. label for ZYNRELEF; the timing of the Company's development of the VAN program and receipt of required regulatory approvals; our ability to establish and maintain successful commercial arrangements like our co-promotion agreement CrossLink Life Sciences; the outcome of the Company's pending ANDA litigation; whether the Company is required to write-off any additional inventory in the future; 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 and the risk that future equity financings may be needed; any inability or delay in achieving profitability. Important factors that could cause actual results to differ materially from those in the forward-looking statements are set forth in our most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q, and in our other reports filed with the Securities and Exchange Commission, including under the caption "Risk Factors." 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: Ira Duarte Executive Vice President, Chief Financial Officer Heron Therapeutics, Inc. [email protected] 858-251-4400 SOURCE Heron Therapeutics, Inc.