What changed in this filing

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Item 4. Controls and Procedures

2024-08-06 compared with 2024-05-07 · 72 added, 12 removed, 35 unchanged (71% 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, 2023.

On August 4, 2023, the Company received a Notice Letter 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.

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 Notice Letter 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.

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.

The parties are currently conducting post-trial briefing.

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.

prior to the expiration of 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.

On September 15, 2023, the Company filed a complaint for patent infringement of the CINVANTI Patents against Mylan in the U.S.

1 unchanged sentence

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.

11,744,800.The parties are currently conducting fact discovery.

2 unchanged sentences

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 December16, 2023, the Company received a Notice Letter 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.

(“Mylan’s ANDA for a generic version of APONVIE”) prior to the expiration of the APONVIE patents, which are listed in the Orange Book.

The Notice Letter alleges that the APONVIE 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 APONVIE.

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.

(“Mylan’s ANDA for a generic version of APONVIE”) prior to the expiration of U.S.

and 11,744,800 (the "APONVIE Patents"), which are listed in the Orange Book.

The Mylan December Notice Letter alleges that the APONVIE 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 APONVIE.

On January 11, 2024, the Company filed a complaint for patent infringement of the APONVIE Patents against Mylan in the U.S.

5 unchanged sentences

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 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 CINVANTI patents, which are listed in the Orange Book.

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.

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.

On January 24, 2024, the Company filed a complaint for patent infringement of the CINVANTI Patents against Slayback and a related entity in the U.S.

1 unchanged sentence

The complaint seeks, among other relief, equitable relief enjoining Slayback from infringing those patents.

The parties are currently providing their pleadings for the case.

On July 2, 2024, the U.S.

District Court for the District of New Jersey granted Slayback’s motion to transfer this matter to the U.S.

District Court for the District of Delaware.

The trial in the U.S.

District Court for the District of Delaware is not yet scheduled.

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

1 unchanged sentence

RIS K FACTORS

Our business is subject to various risks, including those described in Item 1A of our Annual Report on Form 10-K for the year ended December 31, 2023.

There have been no material changes from the risk factors disclosed in Item 1A of our Annual Report on Form 10-K.

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.

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) and palonosetron (formerly marketed by Eisai in conjunction with Helsinn Healthcare S.A.

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.

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