What changed in this filing

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Item 4. Controls and Procedures

2025-05-06 compared with 2024-11-12 · 95 added, 71 removed, 37 unchanged (82% of the section changed)

12 unchanged sentences

Except as discussed below, there are no material changes from the legal proceedings previously disclosed in our most recently filed Annual Report on Form 10-K for the year ended December 31, 2024.

On June 14, 2022, the Company received a Notice Letter (the “Fresenius Kabi Notice”) from Fresenius Kabi advising that Fresenius Kabi had submitted an ANDA to the FDA seeking approval to manufacture, use or sell a generic version of CINVANTI in the U.S.

prior to the expiration of U.S.

and 11,173,118 (the “CINVANTI Patents”), which are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (the “Orange Book”).

The Fresenius Kabi Notice alleges that the CINVANTI Patents are invalid, unenforceable and/or will not be infringed by the commercial manufacture, use or sale of the generic product described in Fresenius Kabi’s ANDA.

On July 27, 2022, the Company filed a complaint for patent infringement of the CINVANTI Patents against Fresenius Kabi and a related entity in the U.S.

District Court for the District of Delaware in response to Fresenius Kabi’s ANDA filing.

The complaint seeks, among other relief, equitable relief enjoining Fresenius Kabi from infringing the CINVANTI Patents.

On May 15, 2024, the Court granted partial summary judgment of infringement for the Company and found no indefiniteness of U.S.

9,561,229 and 9,974,794.

On June 24, 2024, the parties completed a four-day bench trial centered on Fresenius’s defense of obviousness of claims from U.S.

9,561,229 and 9,974,794 that cover CINVANTI.

Oral argument was held on August 29, 2024.

The parties are currently awaiting the Court’s decision.

The Company intends to vigorously enforce its intellectual property rights relating to CINVANTI.

As a result of filing our complaint for patent infringement, the FDA may not approve Fresenius’s ANDA until the earlier of December 14, 2024 or resolution of the litigation.

On August 4, 2023, the Company received a Notice Letter (the “Mylan August Notice”) from Mylan Pharmaceuticals Inc.

(“Mylan”) advising that Mylan had submitted an ANDA to the FDA seeking approval to manufacture, use or sell a generic version of CINVANTI (“Mylan’s ANDA for a generic version of CINVANTI”) in the U.S.

prior to the expiration of the CINVANTI Patents, which are listed in the Orange Book.

(“Mylan”) advising that Mylan had submitted an abbreviated new drug application ("ANDA") to the FDA seeking approval to manufacture, use or sell a generic version of CINVANTI (“Mylan’s ANDA for a generic version of CINVANTI”) in the U.S.

prior to the expiration of U.S.

and 11,173,118 (the “CINVANTI Patents”), which are listed in the Orange Book.

The Mylan August Notice alleges that the CINVANTI Patents are invalid, unenforceable and/or will not be infringed by the commercial manufacture, use or sale of the generic product described in Mylan’s ANDA for a generic version of CINVANTI.

2 unchanged sentences

The complaint seeks, among other relief, equitable relief enjoining Mylan from infringing the CINVANTI Patents.

On November 9, 2023, the Company received an updated Notice Letter from Mylan advising that it had submitted an amendment to Mylan’s ANDA to include a paragraph IV certification to Heron’s recently listed U.S.

The parties completed fact discovery and are progressing into expert discovery.

A five-day bench trial is scheduled for May 19, 2025.

The Company intends to vigorously enforce its intellectual property rights relating to CINVANTI.

As a result of filing our complaint for patent infringement, the FDA may not approve Mylan’s ANDA for a generic version of CINVANTI until the earlier of February 4, 2026 or resolution of the litigation.

On November 9, 2023, the Company received an updated Notice Letter from Mylan advising that it had submitted an amendment to Mylan’s ANDA for a generic version of CINVANTI to include a Paragraph IV certification to the Company's recently listed U.S.

On May 6, 2025, the Company announced that it entered into a settlement agreement with Mylan to resolve the ongoing patent litigation in the U.S.

District Court for the District of Delaware related to Mylan’s ANDA for a generic version of CINVANTI.

Pursuant to the terms of the settlement agreement, the Company has granted Mylan a license under the Orange Book-listed patents for CINVANTI to market a generic version of CINVANTI in the United States beginning June 1, 2032, or earlier under certain customary circumstances.

In connection with the settlement, the Company and Mylan will file a proposed Stipulation and Order of Dismissal with the U.S.

District Court for the District of Delaware requesting that the Court dismiss the pending litigation between the parties.

On December 16, 2023, the Company received a Notice Letter (the “Mylan December Notice”) from Mylan advising that Mylan had submitted an ANDA to the FDA seeking approval to manufacture, use or sell a generic version of APONVIE in the U.S.

6 unchanged sentences

On January 26, 2024, the Court consolidated this litigation concerning Mylan’s ANDA for a generic version of APONVIE with the previously-filed litigation concerning Mylan’s ANDA for a generic version of CINVANTI.

Accordingly, a five-day bench trial is scheduled for May 19, 2025.

The Company intends to vigorously enforce its intellectual property rights relating to APONVIE.

As a result of filing our complaint for patent infringement, the FDA may not approve Mylan’s ANDA for a generic version of APONVIE until the earlier of June 16, 2026 or resolution of the litigation.

On December 12, 2023, the Company received a Notice Letter (the “Slayback Notice”) from Slayback Pharma LLC (“Slayback”) advising that Slayback had submitted an NDA under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act to the FDA seeking approval to manufacture, use or sell a generic version of CINVANTI in the U.S.

(“Slayback’s NDA”) prior to the

expiration of the patents, listed in the Orange Book.

On May 6, 2025, the Company announced that it entered into a settlement agreement with Mylan to resolve the ongoing patent litigation in the U.S.

District Court for the District of Delaware related to Mylan’s ANDA for a generic version of APONVIE.

Pursuant to the terms of the settlement agreement, the Company has granted Mylan a license under the Orange Book-listed patents for APONVIE to market a generic version of APONVIE in the United States beginning June 1, 2032, or earlier under certain customary circumstances.

In connection with the settlement, the Company and Mylan will file a proposed Stipulation and Order of Dismissal with the U.S.

District Court for the District of Delaware requesting that the Court dismiss the pending litigation between the parties.

On December 11, 2023, the Company received a Paragraph IV notice of certification (the “Slayback Notice”) from Slayback Pharma LLC ("Slayback") (now owned by Azurity Pharmaceuticals, Inc.

("Azurity")) advising that Slayback had submitted an new drug application under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act to the FDA seeking approval to manufacture, use or sell a generic version of CINVANTI in the U.S.

(“Slayback’s NDA”) prior to the expiration of the patents listed in the Orange Book.

The Slayback Notice alleges that the CINVANTI Patents are invalid, unenforceable and/or will not be infringed by the commercial manufacture, use or sale of the generic product described in Slayback’s NDA.

5 unchanged sentences

District Court for the District of Delaware.

A four-day bench trial is scheduled for January 20, 2026.

On December 12, 2024, the Company filed a

complaint against Slayback, Azurity, and related entities in the U.S.

District Court for District of Delaware for patent infringement of the U.S.

12,115,254 and 12,115,255.

The parties are currently entering into expert discovery.

A four-day bench trial is currently scheduled for November 17, 2025.

The Company intends to vigorously enforce its intellectual property rights relating to CINVANTI.

As a result of filing our complaint for patent infringement, the FDA may not approve Slayback's NDA until the earlier of June 12, 2026, or resolution of the litigation.

As a result of our initial complaint for patent infringement, the FDA may not approve Slayback’s NDA until the earlier of June 12, 2026 or resolution of the litigation.

On February 28, 2025, Azurity, Azurity Pharma India LLP, and Slayback requested Post-Grant Review ("PGR") of U.S.

12,115,254 and 12,115,255 in PGR2025-00035 and PGR2025-00036, respectively.

On April 14, 2025, the Petitions were accorded a filing date.

The Company’s Patent Owner Preliminary Response is due on July 14, 2025.

On February 7, 2025, the Company received a Notice Letter (the “Qilu Notice”) from Qilu Pharmaceutical (Hainan) Co., Ltd and Qilu Pharma, Inc.

(“Qilu”) advising that Qilu had submitted an ANDA to the FDA seeking approval to manufacture, use or sell a generic version of APONVIE in the U.S.

(“Qilu’s ANDA”) prior to the expiration of U.S.

11,744,800, 12,115,254, and 12,115,255 (the “Noticed APONVIE Patents”), which are listed in the Orange Book, Qilu's ANDA alleges that the Noticed APONVIE Patents are invalid, unenforceable and/or will not be infringed by the commercial manufacture, use or sale of the generic product described in Qilu’s ANDA for a generic version of APONVIE.

On March 21, 2025, the Company filed a complaint for patent infringement of the Noticed APONVIE Patents against Qilu in the U.S.

District Court for the District of Delaware in response to Qilu's ANDA for a generic version of APONVIE.

The complaint seeks, among other relief, equitable relief enjoining Qilu from infringing the Noticed APONVIE Patents.

The case is in its early stages and a trial has not yet been scheduled.

The Company intends to vigorously enforce its intellectual property rights relating to APONVIE.

As a result of filing our complaint for patent infringement, the FDA may not approve Qilu’s ANDA for a generic version of APONVIE until the earlier of August 7, 2027 or resolution of the litigation.

RIS K FACTORS

We operate in a rapidly changing environment that involves a number of risks that could materially affect our business, financial condition or future results, some of which are beyond our control.

In addition to the other information set forth in this report, the risks and uncertainties that we believe are most important for you to consider are discussed in Part I, “Item 1A.

Risk Factors” in the 2023 Form 10-K and in Part II, “Item 1A.

In addition to the other information set forth in this Quarterly Report on Form 10-Q, the risks and uncertainties that we believe are most important for you to consider are discussed in Part I, Item 1A.

"Risk Factors” in the 2024 Annual Report and in Part II, Item 1A.

"Risk Factors” in our subsequently filed Quarterly Reports on Form 10-Q.

Other than the factors set forth below, there have been no material changes to the risk factors described in the 2023 Form 10-K.

We face intense competition from other companies developing products for the management of postoperative pain or the prevention of CINV and PONV.

ZYNRELEF competes in the postoperative pain management market with MARCAINETM (bupivacaine hydrochloride injection, solution, marketed by Pfizer Inc.) and generic forms of bupivacaine;

NAROPIN® (ropivacaine, marketed by Fresenius Kabi USA, LLC) and generic forms of ropivacaine;

EXPAREL® (bupivacaine liposome injectable suspension, marketed by Pacira BioSciences, Inc.);

XARACOLL®(bupivacaine HCl implant, marketed by Innocoll Pharmaceuticals Limited);

POSIMIR® (owned by Durect Corporation and to be marketed in the U.S.

by Innocoll Pharmaceuticals Limited);

ANJESO® (meloxicam injection, marketed by Baudax Bio, Inc.);

OFIRMEV® (acetaminophen injection, marketed by Mallinckrodt Pharmaceuticals);

SEGLENTIS® (celecoxib and tramadol hydrochloride, marketed by Kowa Pharmaceuticals America, Inc.

in the U.S.);

generic forms of IV acetaminophen;

and potentially other products in development for postoperative pain management that reach the U.S.

APONVIE competes in the PONV prevention market with generic ondansetron, the current standard of care, generic aprepitant, and BARHEMSYS® (amisulpride, marketed by Eagle Pharmaceuticals, Inc.);

TAK-951 (a peptide agonist under development (PH2) by Takeda Pharmaceutical Company Limited for PONV and not approved anywhere globally for any use);

and potentially other products in development for PONV prevention that reach the market.

CINVANTI faces significant competition.

NK1 receptor antagonists are administered for the prevention of CINV, in combination with 5-HT3 receptor antagonists, to augment the therapeutic effect of the 5-HT3 receptor antagonist.

Currently available NK1receptor antagonists include:

generic versions of EMEND® IV (fosaprepitant);

EMEND® IV (fosaprepitant, marketed by Merck & Co., Inc.);

EMEND® (aprepitant, marketed by Merck & Co., Inc.);

AKYNZEO®(palonosetron, a 5-HT3 receptor antagonist, combined with netupitant, an NK1 receptor antagonist, marketed by Helsinn Therapeutics (U.S.), Inc.);

VARUBI® (rolapitant, marketed by TerSera Therapeutics LLC), FOCINVEZ TM (fosaprepitant injection, marketed by Amneal Pharmaceuticals, LLC) and other products that include an NK1 receptor antagonist that reach the market for the prevention of CINV.

SUSTOL faces significant competition.

Currently available 5-HT3 receptor antagonists include:

AKYNZEO® (palonosetron, a 5-HT3 receptor antagonist, combined with netupitant, an NK1 receptor antagonist, marketed by Helsinn Therapeutics (U.S.), Inc.);

SANCUSO® (granisetron transdermal patch, marketed by Cumberland Pharmaceuticals Inc.);

and generic products including ondansetron (formerly marketed by GlaxoSmithKline plc as ZOFRAN), granisetron (formerly marketed by Hoffman-La Roche, Inc.

as KYTRIL), palonosetron (formerly marketed by Eisai in conjunction with Helsinn Healthcare S.A.

as ALOXI) and Posfrea (Palonosetron Injection, marketed by AVYXA).

Currently, palonosetron is the only 5-HT3receptor antagonist other than SUSTOL that is approved for the prevention of delayed CINV associated with MEC regimens.

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, which is considered to be a HEC regimen by the NCCN and ASCO.

No other 5-HT3 receptor antagonist is specifically approved for the prevention of delayed CINV associated with a HEC regimen.

Small or early-stage companies and research institutions may also prove to be significant competitors, particularly through collaborative arrangements with large and established pharmaceutical companies.

We will also face competition from these parties in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical trials, and acquiring and in-licensing technologies and products complementary to our programs or potentially advantageous to our business.

If any of our competitors succeed in obtaining approval from the FDA or other regulatory authorities for their product candidates sooner than we do for our product candidates that are more effective or less costly than ours, our commercial opportunity could be significantly reduced.

Major technological changes can happen quickly in the biotechnology and pharmaceutical industries, and the development of technologically improved or different products or drug delivery technologies may make our product candidates or platform technologies obsolete or noncompetitive.

Other than the factors set forth below, there have been no material changes to the risk factors described in the 2024 Annual Report.

Certain of the components used in the manufacture of our Products are, or might be, sourced from a single vendor, and the loss or disruption of this vendor could significantly harm our business.

Some of the critical materials and components used in manufacturing our Products are, or might be, sourced from single suppliers.

An interruption in the supply of a key material could significantly delay our research and development process or increase our expenses for commercialization or development products.

Specialized materials must often be manufactured for the first time for use in drug delivery technologies, or materials may be used in these technologies in a manner different from their customary commercial uses.

The quality of materials can be critical to the performance of a drug delivery technology, so a reliable source that provides a consistent supply of materials is important.

Materials or components needed for our drug delivery technologies may be difficult to obtain on commercially reasonable terms, particularly when relatively small quantities are required or if the materials traditionally have not been used in pharmaceutical products.

Our reliance on a single vendor for certain components used in the manufacturing of our Products also subjects our business to risk associated with the geographic areas in which those single vendors reside, which could include natural or man-made disasters, including severe weather, epidemics, pandemics, acts of war or terrorism, armed conflict, resource shortages, or geopolitical instability, including as a result of increased tariffs and changing regulations and policies that may disrupt global markets or escalate tensions between countries.

Such adverse events could cause global supply chain interruptions that could increase our costs and, to the extent such interruptions impair our ability to have sufficient inventory, cause us to lose revenue or market share.

We continually evaluate our supply chains to identify potential risks and needs for additional manufacturers and other suppliers for the manufacturing of our Products.

Establishing additional or replacement suppliers for certain raw materials in our proprietary polymers, if required, may not be accomplished quickly, or at all, and may involve significant expense.

If we are able to find a replacement supplier, we would need to evaluate and qualify such replacement vendor and its ability

to meet quality and compliance standards.

Any change in suppliers or the manufacturing process for our Products could require additional regulatory approval and result in operational delays.

Some of our suppliers may experience disruption to their respective supply chains due to the adverse events or conditions, including the effects of a pandemic or disease outbreak, the imposition of tariffs and other trade protective measures, rising geopolitical tensions, armed conflict or other factors, which could delay, prevent or impair our development or commercialization efforts.

We obtain certain critical materials and components used in manufacturing our Products from third-party suppliers whose operations might be directly or indirectly affected by adverse events or conditions, including the effects of a pandemic or disease outbreak, the imposition of tariffs and other trade protective measures, rising geopolitical tensions, armed conflict or other factors (including, without limitation, adverse weather conditions, political instability, war, civil unrest, economic instability, outbreaks of disease, or other public health emergencies and the impact of any such U.S.

or foreign government response and public fears regarding any of the foregoing).

For example, the recent increase in retaliatory tariffs between the U.S.

and certain countries, most notably China, has escalated geopolitical tensions and may significantly disrupt the global markets and supply chains.

Further, in recent years, tensions between mainland China and Taiwan have further escalated, with China accelerating the development of military capabilities and threatening the use of military force to gain control over Taiwan in certain circumstances.

Similarly, the geopolitical conflicts in Russia and Ukraine and the Middle East remain unpredictable and could escalate into a broader armed conflict and additional economic sanctions or countermeasures by the affected countries or others, which could exacerbate market and economic instability.

If we are unable to obtain these critical materials and components in sufficient quantities and in a timely manner, the manufacture, development, testing and clinical study of our Products might be delayed or infeasible, which could significantly harm our business.

Changes in government policies, laws, and regulations and with respect to the government workforce may have a negative impact on our business and the markets in which we operate.

The laws and regulations governing our operations, as well as their interpretation, may change from time to time, and new laws and regulations may be enacted.

Similarly, operational changes at government agencies, including actions intended to reduce government spending at agencies that regulate significant parts of our business, such as the FDA and CMS, could have a significant impact on the implementation of laws and regulations that impact our business.

For example, in April 2025, the U.S.

administration conducted significant layoffs at several U.S.

health agencies, including the FDA, the Department of Health and Human Services (the “HHS”), the Centers for Disease Control and Prevention and the National Institutes of Health, which is expected to impact the FDA’s ability to review and approve new medicines and conduct necessary inspections.

The HHS has also proposed a potential major reorganization of the FDA by consolidating product centers for drugs, biologics, devices, tobacco and veterinary medicine, which regulate different product types under distinct rules and regulations and operate under different review processes and timelines for product approval.

Over the last several years, the U.S.

government has also shut down several times and certain regulatory agencies, such as the FDA and SEC, have had to furlough critical employees and stop critical activities.

In addition, government funding of agencies on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable.

There is also a great degree of uncertainty related to the impact of recent U.S.

Supreme Court decisions and executive orders on the FDA’s enforcement and decision-making authority.

In February 2025, President Trump signed an executive order asserting greater authority over all federal agencies, including those established by Congress as independent from direct presidential control.

The executive order may lead to delays, if not cancellations, of pending and proposed regulations at federal agencies and introduces uncertainty as it subjects all significant regulatory actions by the agencies to the President’s supervision and control.

Accordingly, any change in these laws or regulations, changes in their interpretation, or newly enacted laws or regulations and any failure by us to comply with these laws or regulations could require changes to certain of our business practices, negatively impact our operations, cash flow or financial condition, impose additional costs on us or otherwise adversely affect our business.

For example, U.S.

trade policy under the new administration, including potential new or increased tariffs, along with changing trade policies in China, Mexico, the U.K., Canada, and parts of Europe, may impact global trade, create sourcing challenges with respect to raw materials and instruments and increase our costs, potentially harming our business.

In April 2025, the U.S.

administration imposed increased tariffs on all countries and individualized “reciprocal” higher tariffs on certain countries, most notably China, for which other countries responded by announcing retaliatory tariffs on U.S.

The tariff increases have significantly disrupted the global markets and may significantly escalate geopolitical tensions between the U.S.

and other countries, especially China.

Further, in April 2025, the U.S.

Department of Commerce initiated national security investigations into the importation of pharmaceuticals and pharmaceutical ingredients pursuant to Section 232 of the Trade Expansion Act of 1962, which could result in the imposition of new tariffs on imports within the pharmaceutical industry.

The extent of the impact of such tariffs and proposed regulations on our business specifically, or on the U.S.

market and global economy generally, are uncertain and unpredictable, and could adversely affect our business, financial condition and results of operations.

Moreover, uncertainty with respect to legislation, regulation and government policy at the federal, state and local levels, including as a result of the change in administration, has introduced new and difficult-to-quantify macroeconomic and geopolitical risks with potentially far-reaching implications.

With the change in the presidential administration, there are currently a number of laws and regulations in the U.S.

that have recently been adopted but not yet implemented, have been proposed or are being considered to which we or our customers may become subject, including healthcare reform initiatives and potential spending and tax proposals, but at this time their impact on our business and results of operations remains uncertain.

Changes in legislation, regulation or policy increase the likelihood that we will fail to appropriately adapt to changes in our compliance obligations, particularly when such changes happen abruptly, such as following a change in government.

Any of the foregoing changes could increase our litigation and regulatory exposure, directly impact our results of operations and cash flows, adversely affect our ability to provide our products, or adversely impact the demand for our Products.

Such changes may also impact our business by creating increased volatility and uncertainty in the markets in which we operate.

At this time, we cannot predict the ultimate content, timing, or effect of these changes, including any legislative, regulatory and other actions under the new U.S.

administration, or estimate the overall impact of any such changes on our business, results of operations and financial condition.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 4. Controls and Procedures