2 unchanged sentences
Acute Care Product Portfolio
+Added: ZYNRELEF is a dual-acting local anesthetic that delivers a fixed-dose combination of the local anesthetic bupivacaine and a low dose of the nonsteroidal anti-inflammatory drug meloxicam.
+Added: ZYNRELEF is the first and only modified-release local anesthetic to be classified by the FDA as an extended-release product because ZYNRELEF demonstrated 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 FDA in May 2021, and we commenced commercial sales in the U.S.
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ZYNRELEF is approved for small-to-medium open abdominal, lower extremity total joint arthroplasty, soft tissue and orthopedic surgical procedures including foot and ankle, and other procedures in which direct exposure to articular cartilage is avoided.
−Removed: ZYNRELEF is a dual-acting local anesthetic that delivers a fixed-dose combination of the local anesthetic bupivacaine and a low dose of the nonsteroidal anti-inflammatory drug meloxicam.
−Removed: ZYNRELEF is the first and only modified-release local anesthetic to be classified by the FDA as an extended-release product because ZYNRELEF demonstrated 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.
−Removed: In January 2024, we entered into a five-year distributor partnership with CrossLink Life Sciences, LLC (“Crosslink ” ) to expand the sales network supporting ZYNRELEF.
−Removed: Crosslink will be the lead partner in the U.S.
−Removed: to expand ZYNRELEF promotion for orthopedic indications.
−Removed: The partnership will launch in several phases, initially at a regional level, followed by an expanded national rollout.
−Removed: In total, approximately 650 representatives will be added to Heron ’ s sales network over the year.
−Removed: In the fourth quarter of 2022, we validated large-scale manufacturing of our proprietary polymer and ZYNRELEF, which will allow for the manufacturing of ZYNRELEF annually at a significantly reduced cost of product sales.
+Added: In September 2024, the FDA approved our Prior Approval Supplement Application for ZYNRELEF Vial Access Needle ("VAN"), which will replace the current vented vial spike.
In March 2022, the Centers for Medicare and Medicaid Services (“CMS”) approved a 3-year transitional pass-through status of ZYNRELEF, which became effective on April 1, 2022, for separate reimbursement outside of the surgical bundle payment in the Hospital Outpatient Department (“HOPD”) setting of care.
In addition, in December 2022, H.R.
−Removed: 2617, the omnibus spending bill was approved by Congress that includes a provision requiring CMS to pay for certain non-opioids outside the existing bundled payment for surgeries for the period January 1, 2025 through December 31, 2027.
−Removed: ZYNRELEF was granted a marketing authorization by the European Commission in September 2020 and by the United Kingdom ( “ U.K.
−Removed: ” ) Regulatory Authority in January 2021.
−Removed: In August 2023, we cancelled the U.K.
−Removed: ZYNRELEF marketing authorization and, in October 2023, we cancelled the ZYNRELEF marketing authorization in the European Union (“EU ” ) as we do not plan to commercially launch ZYNRELEF in the U.K., the EU, or the other countries in the European Economic Area.
−Removed: Health Canada issued a Notice of Compliance to commercialize ZYNRELEF in March 2022.
−Removed: In the second quarter of 2023, we withdrew our new drug submission, as we do not plan to commercially launch ZYNRELEF in Canada.
+Added: 2617, the omnibus spending bill was approved by Congress, which includes the Non-Opioids Prevent Addiction in the Nation (NOPAIN) Act which directs CMS to provide separate Medicare reimbursement for non-opioid treatments that are used to manage pain during surgeries conducted in hospital outpatient departments or in ambulatory surgical centers.
+Added: To qualify, the non-opioid treatment must demonstrate the ability to replace, reduce, or avoid intraoperative or postoperative opioid use or the quantity of opioids prescribed in a clinical trial or through data published in a peer-reviewed journal.
+Added: The hospital outpatient prospective payment system and ambulatory surgical center proposed rule for calendar year 2025 includes ZYNRELEF as a qualifying non-opioid requiring CMS to provide separate Medicare reimbursement in both the hospital outpatient department and ambulatory surgical center settings from January 1, 2025, through December 31, 2027.
+Added: APONVIE is the first and only intravenous (“IV”) formulation of a substance P/neurokinin-1 (“NK1”) receptor antagonist indicated for postoperative nausea and vomiting (“PONV”).
+Added: Delivered via single 30-second IV injection, APONVIE has demonstrated rapid achievement of therapeutic drug levels ideally suited for the surgical setting.
APONVIE was approved by the FDA in September 2022 and became commercially available in the U.S.
in March 2023.
−Removed: APONVIE is indicated for the prevention of postoperative nausea and vomiting (“PONV ” ) in adults.
+Added: APONVIE is indicated for the prevention of PONV in adults.
CMS granted pass-through payment status for APONVIE, effective April 1, 2023.
−Removed: APONVIE is the first and only intravenous (“IV ” ) formulation of a substance P/neurokinin-1 (“NK 1 ”) receptor antagonist indicated for PONV.
−Removed: Delivered via single 30-second IV injection, APONVIE has demonstrated rapid achievement of therapeutic drug levels ideally suited for the surgical setting.
Oncology Care Product Portfolio
−Removed: SUSTOL was approved by the FDA in August 2016, and we commenced commercial sales in the U.S.
−Removed: in October 2016.
−Removed: 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.
−Removed: SUSTOL is an extended-release, injectable 5-hydroxytryptamine type 3 (“5-HT 3 ”) receptor antagonist that utilizes our Biochronomer Technology to maintain therapeutic levels of granisetron for ≥5 days.
−Removed: 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.
−Removed: SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0–24 hours following chemotherapy) and the delayed phase (24–120 hours following chemotherapy).
−Removed: SUSTOL is the first extended-release 5-HT 3 receptor antagonist approved for the prevention of acute and delayed nausea and vomiting associated with both MEC and AC combination chemotherapy regimens.
−Removed: A standard of care in the treatment of breast cancer and other cancer types, AC regimens are among the most commonly prescribed Highly Emetogenic Cancer (“HEC”) regimens, as defined by both the National Comprehensive Cancer Network (“NCCN”) and the American Society of Clinical Oncology (“ASCO”).
−Removed: In February 2017, the NCCN included SUSTOL as a part of its NCCN Clinical Practice Guidelines in Oncology for Antiemesis Version 1.2017.
−Removed: The NCCN has given SUSTOL a Category 1 recommendation, the highest-level category of evidence and consensus, for use in the prevention of acute and delayed nausea and vomiting in patients receiving HEC or MEC regimens.
−Removed: The guidelines now identify SUSTOL as a “preferred” agent for preventing nausea and vomiting following MEC.
−Removed: Further, the guidelines highlight the unique, extended-release formulation of SUSTOL.
−Removed: In January 2018, a product-specific billing code, or permanent J-code (“J-code”), for SUSTOL became available.
−Removed: The new J-code was assigned by CMS and has helped simplify the billing and reimbursement process for prescribers of SUSTOL.
−Removed: CINVANTI was approved by the FDA in November 2017, and we commenced commercial sales in the U.S.
−Removed: in January 2018.
−Removed: 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, a substance NK1 receptor antagonist.
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Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 receptor antagonist 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).
−Removed: CINVANTI is the first and only IV formulation of an NK 1 receptor antagonist indicated for the prevention of acute and delayed nausea and vomiting associated with HEC and nausea and vomiting associated with MEC that is free of synthetic surfactants, including polysorbate 80.
−Removed: NK 1 receptor antagonists are typically used in combination with 5-HT 3 receptor antagonists.
+Added: CINVANTI is the first and only IV formulation of an NK1 receptor antagonist indicated for the prevention of acute and delayed nausea and vomiting associated with Highly Emetogenic Cancer (“HEC”) and nausea and vomiting associated with moderately emetogenic chemotherapy ("MEC") that is free of synthetic surfactants, including polysorbate 80.
+Added: 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 HEC including high-dose cisplatin as a single-dose regimen, delayed nausea and vomiting associated with initial and repeat courses of MEC as a single-dose regimen, and nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen.
+Added: NK1 receptor antagonists are typically used in combination with 5-hydroxytryptamine type 3 (“5-HT3”) receptor antagonists.
The only other injectable NK1 receptor antagonist currently approved in the U.S.
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Results also showed CINVANTI was better tolerated in healthy volunteers than EMEND IV, with significantly fewer adverse events reported with CINVANTI.
−Removed: In January 2019, a J-code for CINVANTI became available.
−Removed: The new J-code was assigned by CMS and has helped simplify the billing and reimbursement process for prescribers of CINVANTI.
−Removed: In February 2019, the FDA approved our Supplemental New Drug Application ( “ sNDA ”) for CINVANTI, for IV use, which expanded the administration of CINVANTI beyond the initially approved administration method (a 30-minute IV infusion) to include a 2-minute IV injection.
−Removed: In October 2019, the FDA approved our sNDA for CINVANTI to expand the indication and recommended dosage to include the 130 mg single-dose regimen for patients receiving MEC.
−Removed: In the fourth quarter of 2022, we validated larger-scale manufacturing of CINVANTI, which significantly reduced the cost of product sales in 2023 and will continue going forward.
+Added: CINVANTI was approved by the FDA in November 2017, and we commenced commercial sales in the U.S.
+Added: in January 2018.
+Added: SUSTOL is the first extended-release 5-HT3 receptor antagonist approved for the prevention of acute and delayed nausea and vomiting associated with both MEC and anthracycline and cyclophosphamide ("AC") combination chemotherapy regimens.
+Added: A standard of care in the treatment of breast cancer and other cancer types, AC regimens are among the most commonly prescribed HEC regimens, as defined by both the National Comprehensive Cancer Network (“NCCN”) and the American Society of Clinical Oncology (“ASCO”).
+Added: 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 MEC or AC combination chemotherapy regimens.
+Added: SUSTOL is an extended-release, injectable 5-HT3 receptor antagonist that utilizes our Biochronomer Technology to maintain therapeutic levels of granisetron for ≥5 days.
+Added: 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.
+Added: SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0–24 hours following chemotherapy) and the delayed phase (24–120 hours following chemotherapy).
+Added: SUSTOL was approved by the FDA in August 2016, and we commenced commercial sales in the U.S.
+Added: in October 2016.
Biochronomer Technology
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When administered, the polymers undergo controlled hydrolysis, resulting in a controlled, sustained release of the pharmacological agent encapsulated within the Biochronomer-based composition.
−Removed: Furthermore, our Biochronomer Technology is designed to permit more than one pharmacological agent to be incorporated, such that multimodal therapy can be delivered with a single administration.
+Added: Furthermore, our Biochronomer Technology is designed to permit more than
+Added: one pharmacological agent to be incorporated, such that multimodal therapy can be delivered with a single administration.
Sales and Marketing
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The sales force is supported by sales management, internal sales support, an internal marketing group and distribution support.
−Removed: In January 2024, we entered into a distributor partnership with Crosslink to expand the sales network supporting ZYNRELEF.
−Removed: Crosslink will be the lead partner in the U.S.
−Removed: to expand ZYNRELEF promotion for orthopedic indications.
−Removed: In total, approximately 650 representatives will be added to Heron’s sales network over the year.
+Added: In January 2024, we entered into a co-promotion agreement with Crosslink Network to expand the sales network supporting ZYNRELEF.
+Added: Crosslink Network is the lead partner in the U.S.
+Added: for ZYNRELEF promotion for orthopedic indications.
Our Products are distributed in the U.S.
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We cannot give any assurances that we can compete effectively with these other biotechnology and pharmaceutical companies.
−Removed: Our Products compete in, and our product candidates, if approved, will compete in, highly competitive markets.
−Removed: Our potential competitors in these markets may succeed in developing products that could render our Products and our product candidates obsolete or noncompetitive.
−Removed: ZYNRELEF competes in the postoperative pain management market with MARCAINE TM (bupivacaine hydrochloride injection, solution, marketed by Pfizer Inc.) and generic forms of bupivacaine;
+Added: Our Products compete in highly competitive markets.
+Added: Our potential competitors in these markets may succeed in developing products that could render our Products obsolete or noncompetitive.
+Added: 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;
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AKYNZEO®(palonosetron, a 5-HT3 receptor antagonist, combined with netupitant, an NK1 receptor antagonist, marketed by Helsinn Therapeutics (U.S.), Inc.);
−Removed: VARUBI ® (rolapitant, marketed by TerSera Therapeutics LLC) and other products that include an NK 1 receptor antagonist that reach the market for the prevention of CINV.
−Removed: SUSTOL faces significant competition.
+Added: VARUBI® (rolapitant, marketed by TerSera Therapeutics LLC), FOCINVEZTM (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.
+Added: SUSTOL also faces significant competition.
Currently available 5-HT3 receptor antagonists include:
3 unchanged sentences
as KYTRIL) and palonosetron (formerly marketed by Eisai in conjunction with Helsinn Healthcare S.A.
+Added: 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.
−Removed: 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.
+Added: 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 MEC or 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.
Manufacturing and Clinical Supplies
−Removed: We do not own or operate manufacturing facilities for the production of commercial or clinical quantities of any product, including our Products and product candidates.
−Removed: We currently rely on a small number of third-party manufacturers to produce compounds used in our product development and commercial activities and expect to continue to do so to meet the preclinical and clinical requirements of our potential products and for all of our commercial needs.
−Removed: We currently have long-term commercial supply agreements with certain third-party manufacturers.
−Removed: Our manufacturing and processing agreements require that all third-party contract manufacturers and processors produce active pharmaceutical ingredients, excipients and finished products in accordance with the FDA’s current Good Manufacturing Practices (“cGMP”) and all other applicable laws and regulations.
−Removed: We maintain confidentiality agreements with potential and existing manufacturers in order to protect our proprietary rights related to our Products, our product candidates and our Biochronomer Technology.
−Removed: Some of the critical materials and components used in manufacturing our Products and our product candidates are sourced from single suppliers.
−Removed: 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 of our Products or product candidates.
+Added: We do not own or operate manufacturing facilities for the production of commercial or clinical quantities of our Products.
+Added: We currently rely on a small number of third-party manufacturers to produce compounds used in our product development and commercial activities and expect to continue to do so to meet the preclinical and clinical requirements of our Products and potential products and for all of our commercial needs.
+Added: We currently have long-term manufacturing and processing agreements with certain third-party manufacturers.
+Added: These agreements require that all third-party contract manufacturers and processors produce active pharmaceutical ingredients, excipients and finished products in accordance with the FDA’s current Good Manufacturing Practices (“cGMP”) and all other applicable laws and regulations.
+Added: We maintain confidentiality agreements with potential and existing manufacturers in order to protect our proprietary rights related to our Products and our Biochronomer Technology.
+Added: Some of the critical materials and components used in manufacturing our Products are sourced from single suppliers.
+Added: 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 of our Products.
Specialized materials must often be manufactured for the first time for use in drug delivery technologies, or materials may be used in the technologies in a manner that is different from their customary commercial uses.
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We intend for these patent applications to cover, where possible, claims for composition of matter, medical uses, processes for preparation and formulations.
+Added: Our policy is to actively seek patent protection in the U.S.
+Added: and to pursue equivalent patent claims in selected foreign countries, thereby seeking patent coverage for novel technologies and compositions of matter that may be commercially important to the development of our business.
+Added: Granted patents include claims covering the product composition, methods of use and methods of preparation.
+Added: Our existing patents may not cover future products,
+Added: additional patents may not be issued and current patents, or patents issued in the future, may not provide meaningful protection or prove to be of commercial benefit.
We have filed a number of U.S.
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patents and an additional 124 issued (or registered) foreign patents.
−Removed: The patents on the bioerodible technologies expire in March 2026.
−Removed: Currently, CINVANTI is covered by 10 patents issued in the U.S.
+Added: The patents on the bioerodible technologies expire in April 2026.
+Added: CINVANTI is covered by 12 patents issued in the U.S.
and by five patents issued (or registered) in foreign countries including Korea and Japan.
1 unchanged sentence
Foreign patents covering CINVANTI have expiration dates ranging from September 2035 to February 2036.
−Removed: Currently, SUSTOL is covered by 6 patents issued in the U.S.
−Removed: and by 18 patents issued (or registered) in foreign countries including France, Germany, Hong Kong, Ireland, Italy, Japan, Spain, Sweden, Switzerland, Taiwan, and the United Kingdom.
−Removed: patents covering SUSTOL expire in September 2024;
+Added: SUSTOL is covered by 18 patents issued (or registered) in foreign countries including France, Germany, Hong Kong, Ireland, Italy, Japan, Spain, Sweden, Switzerland, Taiwan, and the United Kingdom.
Foreign patents covering SUSTOL expire in September 2025.
−Removed: Currently, ZYNRELEF is protected by 16 patents issued in the U.S.
+Added: ZYNRELEF is protected by 16 patents issued in the U.S.
and by 100 patents issued (or registered) in foreign countries including Albania, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungary, Iceland, Ireland, Italy, Japan, Korea, Latvia, Lithuania, Luxembourg, Macedonia, Malta, Mexico, Monaco, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Taiwan, Turkey and the United Kingdom.
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Foreign patents covering HTX-034 have expiration dates ranging from November 2033 to November 2036.
−Removed: Our policy is to actively seek patent protection in the U.S.
−Removed: and to pursue equivalent patent claims in selected foreign countries, thereby seeking patent coverage for novel technologies and compositions of matter that may be commercially important to the development of our business.
−Removed: Granted patents include claims covering the product composition, methods of use and methods of preparation.
−Removed: Our existing patents may not cover future products, additional patents may not be issued and current patents, or patents issued in the future, may not provide meaningful protection or prove to be of commercial benefit.
Although we believe that our rights under patent applications we own provide a competitive advantage, the patent positions of pharmaceutical and biotechnology companies are highly uncertain and involve complex legal and factual questions.
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Likewise, if we receive approvals to market and distribute any such products abroad, they would also be subject to extensive foreign government regulation.
−Removed: Compliance with these regulations has not had a material effect on our capital expenditures, earnings, or competitive position to date, but new regulations or amendments to existing regulations to make them more stringent could have such an effect in the future.
+Added: Compliance with these regulations has not had a material effect on our capital
+Added: expenditures, earnings, or competitive position to date, but new regulations or amendments to existing regulations to make them more stringent could have such an effect in the future.
We cannot estimate the expenses we may incur to comply with potential new laws or changes to existing laws, or the other potential effects these laws may have on our business.
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and Clinical Trial Applications (“CTAs”) in the EU, and we may file additional INDs and CTAs in the future.
−Removed: We cannot assure that submission of any additional INDs or CTAs for any of our product candidates will result in authorization to commence clinical trials.
+Added: We cannot assure that submission of any additional INDs or CTAs for any of our Products will result in authorization to commence clinical trials.
Clinical Trials
19 unchanged sentences
Additional studies and follow-up may be conducted to document a clinical benefit where drugs are approved under accelerated approval regulations and based on surrogate endpoints.
−Removed: In clinical trials, surrogate endpoints are alternative measurements of the symptoms of a disease or condition that are substituted for
−Removed: measurements of observable clinical symptoms.
+Added: In clinical trials, surrogate endpoints are alternative measurements of the symptoms of a disease or condition that are substituted for measurements of observable clinical symptoms.
In the U.S., failure to timely conduct Phase 4 clinical trials and follow-up could result in withdrawal of approval for products approved under accelerated approval regulations.
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If the 505(b)(2) applicant can establish that reliance on the FDA’s previous approval is scientifically appropriate, it may eliminate the need to conduct certain preclinical studies or clinical trials of the new product.
−Removed: Section 505(b)(2) applications may be submitted for drug products that represent a modification ( e.g.
−Removed: , a new indication or new dosage form) of an eligible approved drug.
+Added: Section 505(b)(2) applications may be submitted for drug products that represent a modification (e.g., a new indication or new dosage form) of an eligible approved drug.
In such cases, the additional information in 505(b)(2) applications necessary to support the change from the previously approved drug is frequently provided by new studies submitted by the applicant.
18 unchanged sentences
Third-party Payor Coverage and Reimbursement
−Removed: Commercial success of our Products and our product candidates that are approved or commercialized for any indication will depend, in part, on the availability of coverage and reimbursement from third-party payors at the federal, state and private levels.
+Added: Commercial success of our Products will depend, in part, on the availability of coverage and reimbursement from third-party payors at the federal, state and private levels.
Government payor programs, including Medicare and Medicaid, private health care insurance companies and managed care plans have attempted to control costs by limiting coverage and the amount of reimbursement for particular procedures or drug treatments.
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We are subject to health care fraud and abuse regulation and enforcement by both the federal government and the states in which we conduct our business.
−Removed: Healthcare providers, physicians and third-party payors play a primary role in the recommendation and prescription of our Products and any other product candidates for which we obtain marketing approval.
−Removed: Arrangements with third-party payors and customers may expose us to applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute our Products and any other product candidates for which we obtain marketing approval.
+Added: Healthcare providers, physicians and third-party payors play a primary role in the recommendation and prescription of our Products.
+Added: Arrangements with third-party payors and customers may expose us to applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute our Products.
Regulations under applicable federal and state healthcare laws and regulations include the federal health care programs’ Anti-Kickback Law, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, in exchange for or to induce either the referral or purchase of any good or service for which payment may be made under federal health care programs such as the Medicare and Medicaid programs.
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Bribery Act, generally prohibit companies and their intermediaries from providing money or anything of value to officials of foreign governments, foreign political parties, or international organizations with the intent to obtain or retain business or seek a business advantage.
−Removed: Recently, there has been a substantial increase in anti-bribery law enforcement activity by U.S.
−Removed: regulators, with more frequent and aggressive investigations and enforcement proceedings by both the DOJ and the U.S.
−Removed: Securities and Exchange Commission (“SEC”).
A determination that our operations or activities are not, or were not, in compliance with U.S.
20 unchanged sentences
Violations of these laws could subject us to strict liability, fines or liability to third parties.
+Added: There are a number of proposed and pending rules and regulations relating to climate-related disclosures to which we may be subject if such rules become effective and survive pending legal challenges.
+Added: For example on March 6, 2024, the U.S.
+Added: Securities and Exchange Commission (the "SEC") adopted a final rule requiring public companies to include various climate-related disclosures in certain documents filed with the SEC, including climate-related financial statement metrics, greenhouse gas emissions and climate related targets and goals, and management's role in managing material climate-related risks.
+Added: A number of state legislators and regulators have adopted or are currently considering proposing or adopting other rules, regulations, directives, initiatives and laws requiring climate-related disclosures or limiting (or affirmatively requiring) certain climate-related conduct, including California laws S.B.
+Added: 261, and A.B.
+Added: The Company is monitoring the status of such regulations.
We are subject to a variety of financial disclosure and securities trading regulations as a public company in the U.S., including laws relating to the oversight activities of the SEC and the regulations of The Nasdaq Capital Market, on which our shares are traded.
1 unchanged sentence
Human Capital Management
−Removed: Heron Employees
−Removed: As of December 31, 2023, Heron employed 126 full-time employees, 72 of whom are involved in sales and marketing activities, 39 of whom are involved in research and development activities and 15 of whom are involved in general and administrative activities.
−Removed: In 2023, Heron reduced headcount, across all functions, in order to enable us to decrease costs and focus our resources on commercial activities to support revenue growth.
−Removed: Our 2023 voluntary turnover rate of 17% was slightly above industry average voluntary turnover due to employee concerns of job stability following our restructuring and extensive leadership changes.
+Added: As of December 31, 2024, we employed 122 full-time employees, 75 of whom are involved in sales and marketing activities, 12 of whom are involved in research and development activities and 35 of whom are involved in general and administrative activities.
None of our employees are represented by a labor union or covered by a collective bargaining agreement.
−Removed: We expect to hire a small number of additional employees in 2024 to backfill critical positions, but do not expect significant headcount growth.
We continually evaluate business needs and opportunities in addition to balancing in-house expertise and capacity with that of outsourced resources.
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Pharmaceutical companies both large and small compete for a limited number of qualified applicants to fill specialized positions, which continued in 2024, with heavy competition for talent.
−Removed: To attract qualified applicants, Heron offers a total rewards package consisting of base salary and cash bonus incentive targets aligned with the applicable market norms, equity compensation, and a comprehensive health and welfare benefits package for every employee.
+Added: To attract qualified applicants, we offer a total rewards package consisting of base salary and cash bonus incentive targets aligned with the applicable market norms and long term equity compensation.
Bonus opportunity and equity compensation increase as a percentage of total compensation based on level of responsibility.
−Removed: Actual bonus payouts for all employees except our most senior executives are based on a weighting of Company and individual performance, which varies based on level of responsibility.
−Removed: Actual bonus payout for our most senior executives is based exclusively on Company performance, as will be more fully described in our Definitive Proxy Statement to be filed with the SEC related to our 2024 Annual Meeting of Stockholders.
−Removed: Heron supports our employees’ further development with individualized development plans, mentoring, coaching, internal development workshops, and certain financial support, including company-paid external conference attendance and tuition reimbursement.
−Removed: Heron sponsors professional society memberships for all employees, as well as memberships for interested female employees in a women’s advocacy organization supporting women in Science, Technology, Engineering and Math.
+Added: Actual bonus payouts for all employees except our executive officers are based on a weighting of Company and individual performance, which varies based on level of responsibility.
+Added: Actual bonus payout for our executive officers (including our named executive officers for the year ended December 31, 2024) is based exclusively on Company performance, as will be more fully described in our Definitive Proxy Statement to be filed with the SEC related to our 2025 Annual Meeting of Stockholders.
+Added: As additional means of attracting and retaining appropriate talent, we offer all employees a robust benefits package offering a comprehensive array of benefits including generous employer contributions toward medical, dental, and vision insurance as well as company paid life and disability insurance coverage.
+Added: We also offer a retirement savings plan with a company match and an Employee Stock Purchase Plan.
+Added: We support our employees’ further development with individualized development plans, mentoring, coaching, internal development workshops, and certain financial support, including Company-paid external conference attendance and tuition reimbursement.
+Added: We sponsor professional society memberships for all employees, as well as memberships for interested female employees in a women’s advocacy organization supporting women in Science, Technology, Engineering and Math.
We also monitor employee compliance with applicable laws and regulations through a third-party ethics and compliance hotline system that facilitates anonymous internal and external reporting of complaints or concerns.
We did not receive any complaints during 2024.
−Removed: Heron strives for greater diversity and inclusion through our employment and management practices, as evidenced by an annual third-party demographic analysis indicating that the diversity of our employee population generally reflects the ethnicity, race and gender of the overall available workforce at all job levels.
−Removed: Where underutilization is identified, we remain committed to current and future outreach efforts in place to build employee diversity through our hiring efforts.
−Removed: We are also building diversity in our leadership team.
−Removed: In 2023, 50% of our Section 16 officers were female.
−Removed: We believe diversity is a competitive advantage and through initiatives established in our recruiting strategy and documented in our Affirmative Action Plan, we continued outreach in 2023 to underrepresented candidates for positions undergoing recruitment and will continue doing so on an ongoing basis.
−Removed: Heron also monitors pay practices and decisions to ensure pay equity for minority and female employees when compared to non-minority and male employees in same or similar positions and when considering objective factors related to position qualifications.
−Removed: Heron is committed to upholding basic human rights and complies with all laws and practices that prohibit child labor, forced or indentured labor, human trafficking and unfair wages.
−Removed: Heron’s Injury and Illness Prevention Plan documents procedures to reduce work-related injuries and occupational illnesses.
−Removed: In 2023, Heron had three Occupational Safety and Health Administration-reportable work-related injuries or illnesses.
−Removed: One was related to a COVID-19 infection and resulted in all of the missed workdays reported.
−Removed: We did not experience any work-related deaths.
+Added: We are committed to the safety, health and security of our employees.
+Added: We believe a hazard-free environment is critical for the success of our business.
+Added: Throughout our operations, we strive to ensure that all our employees have
+Added: access to safe workplaces that allow them to succeed in their jobs.
+Added: Our experience and continuing focus on workplace safety has enabled us to preserve business continuity without sacrificing our commitment to keeping our colleagues safe.
Company Information
−Removed: Our principal executive offices are located at 4242 Campus Point Court, Suite 200, San Diego, California 92121, and our telephone number is (858) 251-4400.
+Added: Our principal executive offices are located at 100 Regency Forest Drive, Suite 300, Cary, North Carolina 27518, and our telephone number is (858) 251-4400.
Our website address is www.herontx.com .
−Removed: We make our periodic and current reports available on our website, free of charge, as soon as reasonably practicable after such material is electronically filed with, or furnished to, the SEC.
+Added: We make our periodic and current reports, and any amendments to those reports, available on our website, free of charge, as soon as reasonably practicable after such material is electronically filed with, or furnished to, the SEC.
No portion of our website is incorporated by reference into this Annual Report on Form 10-K.
−Removed: We file our annual, quarterly and special reports, proxy statements and other information with the SEC.
−Removed: Our filings with the SEC are also available to the public on the SEC’s website at http://www.sec.gov .
−Removed: Additional information regarding us, including our audited financial statements and descriptions of our business, is contained in the documents incorporated by reference in this Annual Report on Form 10-K.
−Removed: Our common stock is traded on The Nasdaq Capital Market, under the symbol “HRTX.”
RISK FACTO RS
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Additional discussion of the risks summarized in this risk factor summary, as well as other risks that we face, can be found below.
−Removed: • We are substantially dependent on the commercial success of our Products and our U.S.
−Removed: product candidates, and if these Products and product candidates do not attain market acceptance by healthcare professionals and patients, our business and results of operations will suffer.
−Removed: • If we are unable to develop and maintain sales, marketing and distribution capabilities or enter into agreements with third parties to sell and market our Products or our product candidates, our sales may be adversely affected.
−Removed: • If we cannot establish satisfactory pricing of our Products or product candidates, if approved, that is also acceptable to the U.S.
−Removed: government, insurance companies, managed care organizations and other payors, or arrange for favorable reimbursement policies, our product sales may be adversely affected and our future revenue might suffer.
+Added: • We are substantially dependent on the commercial success of our Products, and if these Products do not attain market acceptance by healthcare professionals and patients, our business and results of operations will suffer.
+Added: • If we cannot maintain satisfactory pricing of our Products, that is also acceptable to the U.S.
+Added: government, insurance companies, managed care organizations and other payors, or arrange for favorable reimbursement policies, our product sales may be adversely affected and our future revenue may suffer.
• If we fail to comply with our reporting and payment obligations under U.S.
governmental pricing and contracting programs, we could be subject to additional reimbursement requirements, penalties and fines, which could have a negative impact on our business, financial condition, and results of operations.
−Removed: • Because the results of preclinical studies and clinical trials are not necessarily predictive of future results, we can provide no assurances that our Products or product candidates will have favorable results in future studies or receive regulatory approval or expansion of approved indications.
−Removed: • Interim, topline or preliminary data from our clinical trials that we announce or publish may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.
−Removed: • Although the FDA might grant Fast Track, Breakthrough Therapy, Priority Review or similar designations to our Products and product candidates, there can be no assurance that any of our Products or product candidates that receive similar designations in the U.S.
−Removed: or in any other regulatory jurisdictions will receive regulatory approval any sooner than other Products or product candidates that do not have such designations, or at all.
+Added: • If our suppliers or contract manufacturers are unable to manufacture in commercially viable quantities, or perform as expected, we could face delays in our ability to commercialize our Products, our costs will increase and sales of our Products , may be severely hindered.
+Added: • 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.
+Added: • We face intense competition from other companies developing products for the management of postoperative pain or the prevention of CINV and PONV, including lower-cost generic products, which may limit our ability to sell our products.
• Our product platforms or product development efforts may not produce safe, efficacious or commercially viable products, and, if we are unable to develop new products, our business may suffer.
−Removed: • We rely on third parties to conduct our preclinical testing and conduct our clinical trials, and their failure to perform their obligations in a timely and competent manner may delay development and commercialization of our Products and product candidates and our business could be substantially harmed.
−Removed: • If our suppliers or contract manufacturers are unable to manufacture in commercially viable quantities, we could face delays in our ability to commercialize our Products and product candidates, our costs will increase and sales of our Product and product candidates, if approved, may be severely hindered.
−Removed: • The global economic instability could have further adverse effects on our business, including our commercialization efforts, supply chain, regulatory activities, clinical development activities and other business operations.
+Added: • If we are unable to recruit and retain skilled employees, we may not be able to achieve our objectives.
+Added: • Our business strategy may include international expansion, acquisitions of other businesses, products or product licenses.
+Added: We may not be able to successfully manage such activities.
+Added: • Our business strategy may include entry into collaborative agreements.
+Added: We may not be able to enter into collaborative agreements or may not be able to negotiate commercially acceptable terms for these agreements.
+Added: • Natural or man-made disasters, including severe weather, epidemics, pandemics, cyber attacks, acts of war or terrorism, armed conflict, federal workforce uncertainty, or resource shortages, could disrupt our investigational drug candidate development and approved drug commercialization efforts or have other negative consequences on our business and adversely affect results.
• We have a history of losses, we expect to generate losses in the near future, and we may never achieve or maintain profitability.
−Removed: • Additional capital may be needed in the future to enable us to implement our business plan, and we may be unable to raise capital, which would force us to limit or cease our operations and related product development programs.
−Removed: • Drug development involves a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results.
−Removed: • Delays in, or suspensions and terminations of, clinical testing could increase our costs and delay our ability to obtain regulatory approval for, and commercialize, our product candidates.
−Removed: • We may not obtain regulatory approval for our product candidates in development.
−Removed: Regulatory approval may also be delayed or revoked or may impose limitations on the indicated uses of a product candidate.
−Removed: If we are unable to obtain regulatory approval for our product candidates in development, our business will be substantially harmed.
−Removed: • Even if our product candidates in development receive regulatory approval, they may still face future development and regulatory difficulties.
−Removed: If we fail to comply with continuing federal, state and foreign regulations, we could lose our approvals to market drugs, and our business would be seriously harmed.
+Added: • Additional capital will be needed in the future to enable us to implement our business plan, and we may be unable to raise capital, which would force us to limit or cease our operations.
+Added: • Provisions contained in our debt instruments limit our ability to incur additional indebtedness.
+Added: • We could be exposed to significant product liability claims that could be time-consuming and costly to defend, divert management attention and adversely impact our ability to obtain and maintain insurance coverage.
+Added: • If any of our services providers are characterized as employees, we would be subject to employment and tax withholding liabilities and other additional costs.
+Added: • The investment of our cash is subject to risks, which may cause losses or adversely affect the liquidity of these investments and our results of operations, liquidity and financial condition.
+Added: • Adverse developments affecting the financial services industry, such as actual events or concerns involving liquidity, defaults or non-performance by financial institutions or transactional counterparties, could adversely affect our current and projected business operations and its financial condition and results of operations.
+Added: • If we fail to comply with continuing federal, state and foreign regulations with respect to our Products for which we obtain regulatory approval, we could lose our approvals to market drugs, and our business would be seriously harmed.
+Added: • The commercial use of our Products may cause unintended side effects or adverse reactions, or incidents of misuse may occur, which could adversely affect our business.
+Added: • The pharmaceutical industry is subject to significant regulation and oversight pursuant to anti-kickback laws, false claims statutes and anti-corruption laws, which may result in significant additional expense and limit our ability to commercialize our Products.
+Added: In addition, any failure to comply with these regulations could result in substantial fines or penalties.
+Added: • We may incur significant liability if it is determined that we are promoting the “off-label” use of drugs or promoting in a non-truthful and misleading way.
+Added: • Health care reform could increase our expenses and adversely affect the commercial success of our Products.
+Added: • Our use of hazardous materials could subject us to liabilities, fines and sanctions.
+Added: • Our employees may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have a negative impact on our business.
+Added: • We are and may become subject to stringent and evolving laws, regulations, rules, contractual obligations, policies and other obligations related to data privacy and security.
+Added: Our actual or perceived failure to comply with such obligations could lead to regulatory investigations or actions, litigation, fines and penalties, disruptions of our business operations, reputational harm, loss of revenue or profits, and other adverse business consequences.
+Added: • Security breaches and other disruptions could compromise our information and expose us to liability, which would cause our business and reputation to suffer.
+Added: • 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.
• If we are unable to adequately protect or enforce our intellectual property rights, we may lose valuable assets or incur costly litigation to protect our rights.
+Added: • We may be subject to claims that we have infringed on the intellectual property rights of others, and any litigation could force us to stop developing or selling potential products and could be costly, divert management attention and harm our business.
+Added: • We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.
• The price of our common stock has been and may continue to be volatile.
+Added: • Our certificate of incorporation, our bylaws and Delaware law contain provisions that could discourage another company from acquiring us and may prevent attempts by our stockholders to replace or remove our current management.
+Added: • Future utilization of net operating loss carryforwards or research and development credit carryforwards may be impaired due to recent changes in ownership.
+Added: • Actions of activist stockholders could impact the pursuit of our business strategies, cause us to incur substantial costs, divert our management’s attention and resources, and adversely affect our business, results of operations, liquidity, financial condition, and the trading price of our common stock.
+Added: • If we identify a material weakness in our internal control over financial reporting, our ability to meet our reporting obligations and the trading price of our common stock could be negatively affected.
+Added: • Because we do not anticipate paying any cash dividends on our common stock in the foreseeable future, capital appreciation, if any, will be the source of gain for our stockholders.
Risks Related to Our Business
−Removed: We are substantially dependent on the commercial success of our Products and our U.S.
−Removed: product candidates, and if these Products and product candidates do not attain market acceptance by healthcare professionals and patients, our business and results of operations will suffer.
−Removed: The success of our business is substantially dependent on our ability to commercialize our Products and our product candidates.
+Added: We are substantially dependent on the commercial success of our Products, and if these Products do not attain market acceptance by healthcare professionals and patients, our business and results of operations will suffer.
+Added: The success of our business is substantially dependent on our ability to achieve market acceptance of our Products.
Although members of our management team have prior experience launching new drugs, ZYNRELEF, APONVIE, CINVANTI and SUSTOL are the first four products that we have launched.
−Removed: Further, even if our sales organization performs as expected, the revenue that we may receive from the sales of our Products and our product candidates, if approved, may be less than anticipated due to factors that are outside of our control.
+Added: Further, even if our sales organization performs as expected, the revenue that we may receive from the sales of our Products, may be less than anticipated due to factors that are outside of our control.
The factors that may affect revenue include:
−Removed: • the scope of our approved Product labels, including our recently expanded indication statement of ZYNRELEF in the U.S.;
+Added: • the scope of our approved Product labels, including any expanded indications;
• the perception of physicians and other members of the health care community of the safety and efficacy and cost-competitiveness relative to that of competing products;
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• our ability to raise patient and physician awareness of PONV associated with surgical procedures and encourage physicians to look for incidence of PONV among patients;
−Removed: • the cost-effectiveness of our Products and our product candidates;
• the timing and scope of acceptance of our Products by institutional formulary committees and the amount of time between such acceptance and the first use of our Products within the applicable setting of care;
−Removed: • patient and physician satisfaction with our Products and our product candidates;
−Removed: • the size of the potential market for our Products and our product candidates;
−Removed: • our ability to obtain adequate reimbursement from government and third-party payors;
−Removed: • unfavorable publicity concerning our Products, our product candidates or similar products;
+Added: • patient and physician satisfaction with our Products;
+Added: • the size of the potential market for our Products;
+Added: • our ability to obtain coverage and adequate reimbursement from government and third-party payors;
+Added: • unfavorable publicity concerning our Products or similar products;
• the introduction, availability and acceptance of competing treatments, including competing generic products;
−Removed: • adverse event information relating to our Products, our product candidates or similar classes of drugs;
−Removed: • product liability litigation alleging injuries relating to our Products, our product candidates or similar classes of drugs;
−Removed: • our ability to maintain and defend our patents and trade secrets for our Products, our product candidates and our Biochronomer Technology;
+Added: • adverse event information relating to our Products or similar classes of drugs;
+Added: • product liability litigation alleging injuries relating to our Products or similar classes of drugs;
+Added: • our ability to maintain and defend our patents and trade secrets for our Products and our Biochronomer Technology;
• our ability to continue to have our Products manufactured at commercial production levels successfully and on a timely basis;
• our ability to scale up manufacturing of our Products to meet commercial requirements;
−Removed: • the availability of raw materials necessary to manufacture our Products and our product candidates;
−Removed: • our ability to access third parties to manufacture and distribute our Products and our product candidates on acceptable terms or at all and those third parties’ ability and/or willingness to fully perform their obligations;
−Removed: • regulatory developments related to the manufacture or continued use of our Products and our product candidates;
+Added: • the availability of raw materials necessary to manufacture our Products;
+Added: • our ability to establish and maintain successful commercial arrangements like our co-promotion agreement with Crosslink Network;
+Added: • our ability to access third parties to manufacture and distribute our Products on acceptable terms or at all and those third parties’ ability and/or willingness to fully perform their obligations;
+Added: • regulatory developments related to the manufacture or continued use of our Products;
• conduct of post-approval study requirements and the results thereof;
−Removed: • the extent and effectiveness of sales and marketing and distribution support for our Products and our product candidates;
+Added: • the extent and effectiveness of sales and marketing and distribution support for our Products;
• our competitors’ activities, including decisions as to the timing of competing product launches, generic entrants, pricing and discounting;
−Removed: • any other material adverse developments with respect to the commercialization of our Products and our product candidates.
−Removed: Our business will be adversely affected if, due to these or other factors, our commercialization of our Products and our product candidates does not achieve the acceptance and demand necessary to sustain revenue growth.
−Removed: If we are unable to successfully commercialize our Products and our product candidates our business and results of operations will suffer.
−Removed: If we are unable to develop and maintain sales, marketing and distribution capabilities or enter into agreements with third parties to sell and market our Products or our product candidates, our sales may be adversely affected.
+Added: • any other material adverse developments with respect to the commercialization of our Products.
+Added: Our business will be adversely affected if, due to these or other factors, our commercialization of our Products does not achieve the acceptance and demand necessary to sustain revenue growth.
+Added: If we are unable to successfully commercialize our Products our business and results of operations will suffer.
+Added: If we are unable to develop and maintain sales, marketing and distribution capabilities or enter into agreements with third parties to sell and market our Products, our sales may be adversely affected.
We have established an internal commercial organization for the sale, marketing and distribution of our Products in the U.S.
−Removed: The development of a sales organization to market our Products and product candidates is expensive and time consuming, and we cannot be certain that we will be able to successfully develop this capacity or that this function will execute as expected.
+Added: The development of a sales organization to market our Products is expensive and time consuming, and we cannot be certain that we will be able to successfully develop this capacity or that this function will execute as expected.
If we are unable to establish and maintain adequate sales, marketing and distribution capabilities, whether independently or with third parties, we may not be able to generate product revenue and our business and results of operations will suffer.
−Removed: Our internal sales and marketing organization is not currently structured or staffed to launch products on an international level and, therefore, we may not be able to successfully commercialize our Products or product candidates outside of the U.S.
−Removed: In order to commercialize our Products or product candidates in jurisdictions other than the U.S., we would be required to obtain separate marketing approvals and comply with numerous and varying regulatory requirements in each foreign country.
−Removed: If we decide to seek the assistance of third parties with international expertise to help commercialize our Products or product candidates outside of the U.S., we may not be successful in finding willing third parties and, even if we are able to find willing third parties, they might not be able to successfully obtain the approvals and take the steps needed to commercialize our Products or product candidates.
−Removed: If we decide to commercialize our Products or product candidates outside of the U.S.
+Added: Our internal sales and marketing organization is not currently structured or staffed to launch products on an international level and, therefore, we may not be able to successfully commercialize our Products outside of the U.S.
+Added: In order to commercialize our Products in jurisdictions other than the U.S., we would be required to obtain separate marketing approvals and comply with numerous and varying regulatory requirements in each foreign country.
+Added: If we decide to seek the assistance of third parties with international expertise to help commercialize our Products outside of the U.S., we may not be successful in finding willing third parties and, even if we are able to find willing third parties, they might not be able to successfully obtain the approvals and take the steps needed to commercialize our Products.
+Added: If we decide to commercialize our Products outside of the U.S.
without the assistance of third parties with international expertise, it may take longer than expected to obtain the approvals and take the steps needed to commercialize them.
−Removed: As a result, we may decide to delay or abandon development efforts in certain
−Removed: Any such delay or abandonment may have an adverse effect on the benefits otherwise expected from marketing our Products or product candidates in foreign countries.
−Removed: If we enter into arrangements with third parties to help commercialize our Products and product candidates, we would be dependent on the subsequent success of these other parties in performing their responsibilities.
−Removed: Such third parties may not perform their obligations under our agreements with them.
−Removed: We cannot control the amount and timing of such third parties' resources that will be devoted to commercializing our Products and product candidates pursuant to our collaborative agreements with them.
−Removed: For example, we have entered into a Co-Promotion Agreement with Crosslink Network, LLC (“Crosslink”) pursuant to which the Company has committed to pay Crosslink certain agreed-upon compensation to co-promote the sale of certain products;
−Removed: however, if Crosslink fails to perform as anticipated for any reason, it could adversely impact our financial condition and be detrimental to our future business prospects.
−Removed: In addition, under the terms of the Co-Promotion Agreement, Crosslink was appointed as the Company’s exclusive co-promoter of ZYNRELEF within the U.S.
−Removed: If we cannot establish satisfactory pricing of our Products or product candidates, if approved, that is also acceptable to the U.S.
+Added: As a result, we may decide to delay or abandon development efforts in certain markets.
+Added: Any such delay or abandonment may have an adverse effect on the benefits otherwise expected from marketing our Products in foreign countries.
+Added: From time to time, we may enter into additional arrangements with third parties to help commercialize our Products and we would be dependent on the subsequent efforts of these other parties to sell our Products.
+Added: Currently, we have a co-promotion agreement with Crosslink Network, pursuant to which we have committed to pay Crosslink Network certain agreed-upon compensation to co-promote the sale of certain products and Crosslink Network has been appointed as our exclusive co-promoter of ZYNRELEF within the U.S.
+Added: If Crosslink Network or any such other third
+Added: party fails to perform their obligations as anticipated for any reason, it could adversely impact our financial condition and be detrimental to our future business prospects.
+Added: If we cannot maintain satisfactory pricing of our Products that is also acceptable to the U.S.
government, insurance companies, managed care organizations and other payors, or arrange for favorable reimbursement policies, our product sales may be adversely affected and our future revenue may suffer.
The continuing efforts of the U.S.
−Removed: government, insurance companies, managed care organizations and other payors of health care costs to contain or reduce costs of health care may adversely affect our ability to generate adequate revenues and gross margins to make our Products or product candidates commercially viable.
−Removed: Our ability to commercialize our Products and product candidates successfully will depend in part on the extent to which governmental authorities, private health insurers and other organizations establish appropriate reimbursement levels for the cost of such products and related treatments and for what uses reimbursement will be provided.
−Removed: Adoption of our Products and product candidates by the medical community may be limited if third-party payors will not offer adequate coverage.
+Added: government, insurance companies, managed care organizations and other payors of health care costs to contain or reduce costs of health care may adversely affect our ability to generate adequate revenues and gross margins to make our Products commercially viable.
+Added: Our ability to commercialize our Products successfully will depend in part on the extent to which governmental authorities, private health insurers and other organizations establish appropriate reimbursement levels for the cost of such products and related treatments and for what uses reimbursement will be provided.
+Added: Adoption of our Products by the medical community may be limited if third-party payors will not offer adequate coverage.
In addition, third-party payors often challenge the price and cost-effectiveness of medical products and services, and such pressure may increase in the future.
In many cases, uncertainty exists as to the adequate reimbursement status of newly approved healthcare products.
−Removed: Accordingly, our Products and product candidates may not be reimbursable by certain third-party payors at the time of commercial launch and potentially for an extended period of time thereafter.
−Removed: In addition, our Products and product candidates may not be considered cost-effective and adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize a profit.
+Added: Accordingly, our Products may not be considered cost-effective and adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize a profit.
Further, coverage policies and third-party payor reimbursement rates may change at any time.
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Legislation and regulations affecting the pricing of pharmaceuticals may change and any such changes could further limit reimbursement.
−Removed: Cost control initiatives may decrease coverage and payment levels for our Products or product candidates and, in turn, the reimbursement that we receive.
−Removed: We are unable to predict all changes to the coverage or reimbursement methodologies that will be applied by private or government payors to our Products or product candidates.
−Removed: If our Products or product candidates do not receive adequate reimbursement, our revenue could be severely limited.
+Added: Cost control initiatives may decrease coverage and payment levels for our Products and, in turn, the reimbursement that we receive.
+Added: We are unable to predict all changes to the coverage or reimbursement methodologies that will be applied by private or government payors to our Products.
+Added: If our Products do not receive adequate reimbursement, our revenue could be severely limited.
In the U.S., given recent federal and state government initiatives directed at lowering the total cost of health care, the U.S.
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Similarly, the SUPPORT Act, which was signed into law on October 24, 2018, established policies to encourage the prevention and treatment of opioid addiction and the development of non-opioid pain management treatments.
−Removed: Currently, due to the SUPPORT Act, Medicare pays separately for certain non-opioid pain management drugs in ambulatory surgical centers (“ASC”) but no in the hospital outpatient setting (“OPPS”).
−Removed: As ZYNRELEF is already separately paid in both settings due to a different policy, the changes from the SUPPORT Act may increase competition for ZYNRELEF.
−Removed: Recently, the Consolidated Appropriations Act of 2023 established a three-year period of separate payment for non-opioid pain relief products in the OPPS and ASC settings for 2025 through 2027.
−Removed: Beginning January 1, 2025, Medicare will provide separate payment via a different methodology than currently for qualified non-opioids for pain relief in the OPPS and ASC settings through December 31, 2027.
−Removed: This new policy could potentially increase access for ZYNRELEF but may increase competition.
+Added: Due to the SUPPORT Act, Medicare pays separately for certain non-opioid pain management drugs in ambulatory surgical centers (“ASC”) but not in the hospital outpatient setting (“OPPS”).
+Added: However, under the Consolidated Appropriations Act of 2023, the prior payment policy was replaced by a new three-year period of separate payment for non-opioid pain relief products in the OPPS and ASC settings for 2025 through 2027.
+Added: As of January 1, 2025, Medicare has implemented this new payment methodology, which remains in effect through December 31, 2027.
+Added: For 2025, ZYNRELEF is included in this new policy, effective April 1, which means continued separate Medicare payment in the OPPS and ASC settings.
+Added: While this change may improve access to ZYNRELEF, it may also lead to greater competition.
In March 2021, Congress enacted the American Rescue Plan Act of 2021, which removed the statutory cap on rebates that manufacturers pay to state Medicaid programs pursuant to the Medicaid Drug Rebate Program.
−Removed: This provision, which takes effect in 2024, may increase our rebate obligations and have a negative impact on our business.
The Infrastructure Investment and Jobs Act, signed into law on November 15, 2021, also included a provision requiring drug manufacturers to pay CMS a refund for certain amounts of Part B drugs that are discarded from a single-dose container or single-use package.
−Removed: Under the law, and a CMS Proposed Rule issued in July 2022, this refund program became effective on January 1, 2023 and could potentially result in refund obligations.
−Removed: Further, the Inflation Reduction Act of 2022 (“IRA”), signed into law in August 2022, includes various provisions intended to address drug-pricing issues (such as provisions empowering the federal government to negotiate the price of some high-cost, single-source Medicare Part B and Part D drugs (with the new pricing to take effect in January 2026 or thereafter) and requiring rebates for certain Part B and Part D drugs if their price increases outpace inflation).
−Removed: Although it is too early to assess the impact of these provisions on our Products and product candidates, our Products would be unlikely to be selected for price negotiation given their low Medicare expenditures relative to other drugs.
−Removed: However, Medicare inflation rebates may impact our product pricing or increase our rebate obligations.
+Added: Under the law, and a CMS Proposed Rule issued in July 2022, this refund program became effective on January 1, 2023.
+Added: Neither of these pieces of legislation have had a material impact on the Company, through December 31, 2024.
+Added: Further, the Inflation Reduction Act of 2022 (“IRA”), signed into law in August 2022, includes various provisions intended to address drug-pricing issues (such as provisions empowering the federal government to negotiate the
+Added: price of some high-cost, single-source Medicare Part B and Part D drugs (with the new pricing to take effect in January 2026 or thereafter) and requiring rebates for certain Part B and Part D drugs if their price increases outpace inflation).
+Added: Although it is too early to assess the impact of these provisions on our Products, our Products would be unlikely to be selected for price negotiation given their low Medicare expenditures relative to other drugs.
+Added: However, Medicare inflation rebates may impact our product pricing or increase our rebate obligations, though no material impact has been observed thus far through December 31, 2024.
In addition, developments in Medicare hospital outpatient reimbursement for 340B-acquired drugs may further drive 340B hospital business for Heron.
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Becerra et al, since January 1, 2023, the Medicare Part B hospital outpatient payment rate for 340B-acquired drugs has returned to being at the same rate as the rate for non-340B hospitals, Average Selling Price (ASP) + 6% methodology.
−Removed: As evidenced by developments such as these, low prices of our Products and product candidates in the U.S.
−Removed: and foreign jurisdictions may have a negative impact on the prices of our Products and product candidates in the U.S.
+Added: As evidenced by developments such as these, low prices of our Products in the U.S.
+Added: and foreign jurisdictions may have a negative impact on the prices of our Products in the U.S.
For example, if legislation is passed or regulations are adopted that tie the prices of U.S.
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State Medicaid programs are increasingly asking manufacturers to pay supplemental rebates and requiring prior authorization by the state program for use of any drug for which supplemental rebates are not being paid.
−Removed: Further, the trend toward managed health care in the U.S., which could significantly influence the purchase of health care services and products, may result in lower prices for our Products and our product candidates, once approved for marketing.
+Added: Further, the trend toward managed health care in the U.S., which could significantly influence the purchase of health care services and products, may result in lower prices for our Products.
While we cannot predict whether any legislative or regulatory proposals affecting our business will be adopted, the announcement or adoption of these proposals could have a material and adverse effect on our potential revenues and gross margins.
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governmental pricing and contracting programs, we could be subject to additional reimbursement requirements, penalties and fines, which could have a negative impact on our business, financial condition, and results of operations.
−Removed: The Medicare program and certain government pricing programs, including the Medicaid drug rebate program, the Public Health Services’ 340B drug pricing program, and the pricing program under the Veterans Health Care Act of 1992 impact the reimbursement we may receive from sales of our Products, our product candidates or any other products that are approved for marketing in the U.S.
+Added: The Medicare program and certain government pricing programs, including the Medicaid drug rebate program, the Public Health Services’ 340B drug pricing program, and the pricing program under the Veterans Health Care Act of 1992 impact the reimbursement we may receive from sales of our Products, or any other products that are approved for marketing in the U.S.
Pricing and rebate calculations vary among programs.
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governmental pricing and contracting programs may result in additional payments, penalties and fines due to government agencies, which could negatively impact our business, financial condition and results of operations.
−Removed: Because the results of preclinical studies and clinical trials are not necessarily predictive of future results, we can provide no assurances that our Products or product candidates will have favorable results in future studies or receive regulatory approval or expansion of approved indications.
−Removed: Positive results from preclinical studies or clinical trials should not be relied on as evidence that later or larger-scale studies will succeed.
−Removed: Even if our Products or product candidates achieve positive results in early-stage preclinical studies or clinical studies, we will be required to demonstrate that they are safe and effective for use in Phase 3 studies before we can seek expanded indications or regulatory approvals for their commercial sale.
−Removed: Even if our early-stage preclinical studies or clinical studies achieve the specified endpoints, the FDA may determine that these data are not sufficient to allow the commencement of Phase 3 studies.
−Removed: There is an extremely high historical rate of failure of product candidates proceeding through clinical trials in our industry.
−Removed: There is no guarantee that the efficacy of any of our product candidates shown in early patient studies will be replicated or maintained in future studies and/or larger patient populations.
−Removed: Similarly, favorable safety and tolerability data seen in short-term studies might not be replicated in studies of longer duration and/or larger patient populations.
−Removed: If any Product or product candidate demonstrates insufficient safety or efficacy in any preclinical study or clinical trial, we would experience potentially significant delays in, or be required to abandon, development of that Product for an expanded indication, or product candidate for approval.
−Removed: In addition, product candidates in Phase 3 studies may fail to show the desired safety and efficacy despite having progressed through preclinical and earlier stage clinical trials, which could delay, limit or prevent regulatory approval.
−Removed: Further, data obtained from pivotal clinical studies are susceptible to varying interpretations, which could delay, limit or prevent regulatory approval.
−Removed: Regulatory approval may also be delayed, limited or prevented by other factors.
−Removed: If we delay or abandon our efforts to develop any of our Products for expanded indications, or product candidates for approval, we may not be able to generate sufficient revenues to become profitable, and our reputation in the industry and in the investment community would likely be significantly damaged, each of which would cause our stock price to decrease significantly.
−Removed: Interim, topline or preliminary data from our clinical trials that we announce or publish may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.
−Removed: We may publicly disclose interim, topline, or preliminary data from our clinical trials, which is based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a full analyses of all data related to the particular trial.
−Removed: We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity to fully and carefully evaluate all data.
−Removed: As a result, the interim, topline, or preliminary results that we report may differ from future results of the same trials, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated.
−Removed: Topline data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published.
−Removed: As a result, topline data should be viewed with caution until the final data are available.
−Removed: We may also disclose interim data from our clinical trials.
−Removed: Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available.
−Removed: Adverse differences between interim, topline or preliminary data and final data could significantly harm our business prospects.
−Removed: Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate or product and our business in general.
−Removed: In addition, the information we choose to publicly disclose regarding a particular study or clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine is the material or otherwise appropriate information to include in our disclosure, and any information we determine not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise regarding a particular drug, product candidate or our business.
−Removed: If the interim, topline, or preliminary data that we report differ from actual results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain expanded indications for our
−Removed: Products, or to obtain approvals for and commercialize our product candidates, our business, operating results, prospects or financial condition may be harmed.
−Removed: Although the FDA might grant Fast Track, Breakthrough Therapy and Priority Review or similar designations to our Products and product candidates, there can be no assurance that any of our Products or product candidates that receive similar designations in the U.S.
−Removed: or in any other regulatory jurisdictions will receive regulatory approval any sooner than other Products or product candidates that do not have such designations, or at all.
−Removed: Fast Track designation is intended to facilitate the development and expedite the review of new therapies to treat serious conditions with unmet medical needs by providing sponsors with the opportunity for frequent interactions with the FDA.
−Removed: Breakthrough Therapy designation is designed to expedite the development and review of drugs that are intended to treat serious conditions and for which preliminary clinical evidence indicates substantial improvement over available therapies on clinically significant endpoint(s).
−Removed: Priority Review designation is for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment or prevention of serious conditions.
−Removed: product candidates that receive Fast Track or Breakthrough Therapy designation may receive more frequent interactions with the FDA regarding the product candidate’s development plan and clinical trials and may be eligible for the FDA’s Rolling Review and Priority Review.
−Removed: Priority Review designation is intended to direct overall attention and resources of the FDA to the evaluation of such applications and means that the FDA’s goal is to take action on such applications within 6 months, compared to 10 months under standard review.
−Removed: We can provide no assurances that any of our Products or product candidates that receive Fast Track, Breakthrough Therapy, Priority Review or similar designations in the U.S.
−Removed: or in any other regulatory jurisdictions will receive regulatory approval any sooner than other Products or product candidates that do not have such designations, or at all.
−Removed: The FDA or any foreign regulatory authorities may also withdraw or revoke Fast Track, Breakthrough Therapy, Priority Review or similar designations, or elect to treat designated candidates in a manner different from what was originally indicated, if they determine that any of our Products or product candidates that receive such designations no longer meet the relevant criteria.
−Removed: Failure to realize the potential benefits of these designations could materially and adversely affect our business, financial condition, cash flows and results of operations.
−Removed: Our product platforms or product development efforts may not produce safe, efficacious or commercially viable products, and, if we are unable to develop new products, our business may suffer.
−Removed: Our long-term viability and growth will depend on the successful development of products through our research and development activities.
−Removed: Product development is very expensive and involves a high degree of risk.
−Removed: Only a small number of research and development programs result in the commercialization of a product.
−Removed: Success in preclinical work or early-stage clinical trials does not ensure that later-stage or larger-scale clinical trials will be successful.
−Removed: Our ability to complete our clinical trials in a timely fashion depends in large part on a number of key factors, including protocol design, regulatory and IRB approval, the rate of patient enrollment in clinical trials and compliance with extensive cGCP.
−Removed: In addition, because we fund the development of our Products and product candidates, we may not be able to continue to fund all such development efforts to completion or to provide the support necessary to perform the clinical trials, obtain regulatory approvals, or market any approved products.
−Removed: If our drug delivery technologies or product development efforts fail to result in the successful development and commercialization of our Products and product candidates, or if our new Products do not perform as anticipated, such events could materially and adversely affect our business, financial condition, cash flows and results of operations.
−Removed: We rely on third parties to conduct our preclinical testing and conduct our clinical trials, and their failure to perform their obligations in a timely and competent manner may delay development and commercialization of our Products and product candidates and our business could be substantially harmed.
−Removed: We have used contract research organizations (“CROs”) to oversee or provide selected services for our clinical trials for our Products and our product candidates, and we expect to use the same or similar organizations for our future clinical trials and pipeline programs.
−Removed: There can be no assurance that these CROs will perform their obligations at all times in a competent or timely fashion, and we must rigorously oversee their activities in order to be confident in their conduct of these trials on our behalf.
−Removed: If the CROs fail to commit resources to our Products or product candidates, our clinical programs could be delayed, terminated or unsuccessful, and we may not be able to obtain
−Removed: initial or expanded regulatory approvals for, or successfully commercialize, them.
−Removed: Different cultural and operational issues in foreign countries could cause delays or unexpected problems with patient enrollment or with the data obtained from those locations.
−Removed: If we experience significant delays in the progress of our clinical trials or experience doubts with respect to the quality of data derived from our clinical trials, we could face significant delays in gaining necessary product approvals.
−Removed: We also rely on third parties to assist in conducting our preclinical studies in accordance with GLP and the Animal Welfare Act requirements.
−Removed: We, our CROs and other third parties are required to comply with cGCP, which are regulations and guidelines enforced by the FDA, the Competent Authorities of the Member States of the EEA and comparable foreign regulatory authorities.
−Removed: Regulatory authorities enforce cGCP through periodic inspections of trial sponsors, principal investigators and trial sites.
−Removed: If we or any of our CROs fail to comply with applicable cGCP, the clinical data generated in the clinical trials may be deemed unreliable, and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications.
−Removed: We cannot be certain that on inspection by a given regulatory authority, such regulatory authority will determine that any of our ongoing or future clinical trials comply with cGCP.
−Removed: In addition, all of our clinical trials must be conducted with product produced under cGMP.
−Removed: Failure to comply with these regulations may require us to repeat preclinical and clinical trials, which would increase our related expenses and delay the regulatory approval process.
−Removed: Our CROs and other third parties we may engage to support our development programs are not our employees, and, except for remedies available to us under our agreements with such CROs, we cannot control whether or not they devote sufficient time and resources to our ongoing clinical, non-clinical and preclinical programs.
−Removed: Outsourcing these functions involves risk that third parties may not perform to our standards, may not produce results in a timely manner, or may fail to perform at all.
−Removed: If CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines or if the quality or accuracy of the preclinical results or clinical data they obtain is compromised due to the failure to adhere to test requirements, our clinical protocols, regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our Products and product candidates.
−Removed: As a result, our results of operations and the commercial prospects for our Products and product candidates would be harmed, our costs could increase and our ability to generate revenues could be delayed.
−Removed: If our suppliers or contract manufacturers are unable to manufacture in commercially viable quantities, we could face delays in our ability to commercialize our Products and product candidates, our costs will increase and sales of our Products and product candidates, if approved, may be severely hindered.
−Removed: If in the future any of our product candidates are approved for commercial sale, we will need to be able to consistently manufacture such product candidates in larger quantities and be able to show equivalency to the FDA, and foreign regulatory authorities, in the manufacture of such product candidates at commercial scale as compared to development batch size.
−Removed: The commercial success of our Products and our product candidates will be dependent on the ability of our contract manufacturers to produce a product in commercial quantities at competitive costs of manufacture in a process that is validated by the FDA.
+Added: If our suppliers or contract manufacturers are unable to manufacture in commercially viable quantities, we could face delays in our ability to commercialize our Products, our costs will increase and sales of our Products , may be severely hindered.
+Added: The commercial success of our Products are dependent on the ability of our contract manufacturers to produce a product in commercial quantities at competitive costs of manufacture in a process that is validated by the FDA.
We have scaled up manufacturing for CINVANTI and ZYNRELEF in order to realize important economies of scale, and these activities took time to implement, required additional capital investment, process development and validation studies and regulatory approval.
We cannot guarantee that we will be successful in achieving competitive manufacturing costs through such scaled-up activities or that our contract manufacturers will perform their obligations.
−Removed: In addition, our manufacturing agreements include payment terms that require significant cash payments at specified times, and if we are unable to make the required payments at the required times, we are at risk of default under the agreements, which would severely hinder our ability to procure adequate amounts of our Products or product candidates.
+Added: In addition, our manufacturing agreements include payment terms that require significant cash payments at specified times, and if we are unable to make the required payments at the required times, we are at risk of default under the agreements, which would severely hinder our ability to procure adequate amounts of our Products.
The manufacture of pharmaceutical products is a highly complex process in which a variety of difficulties may arise, including product loss due to material failure, equipment failure, vendor error, operator error, labor shortages, inability to obtain material, equipment or transportation, physical or electronic security breaches and natural or man-made disasters.
−Removed: Problems with manufacturing processes could result in product defects or manufacturing failures, which could require us to delay shipment of products or recall products previously shipped, or could impair our
−Removed: ability to expand into new markets or supply products in existing markets.
+Added: Problems with manufacturing processes could result in product defects or manufacturing failures, which could require us to delay shipment of products or recall products previously shipped, or could impair our ability to expand into new markets or supply products in existing markets.
We may not be able to resolve any such problems in a timely manner, if at all.
−Removed: We depend on third-party suppliers and contract manufacturers to manufacture our Products and our product candidates, and we expect to do the same for any future products that we develop;
+Added: We depend on third-party suppliers and contract manufacturers to manufacture our Products, and we expect to do the same for any future products that we develop;
if our contract manufacturers do not perform as expected, our business could suffer.
−Removed: We do not own or operate manufacturing facilities for the production of commercial or clinical quantities of any product, including our Products and our product candidates.
−Removed: Our ability to successfully commercialize our Products and our product candidates depends in part on our ability to arrange for and rely on other parties to manufacture our products at a competitive cost, in accordance with regulatory requirements, and in sufficient quantities for clinical testing and eventual commercialization.
−Removed: We currently rely on a small number of third-party manufacturers to produce compounds used in our product development activities and expect to continue to do so to meet the preclinical and clinical requirements of our potential products and for all of our commercial needs.
−Removed: Certain contract manufacturers are, at the present time (and are expected to be for the foreseeable future), our sole resource to manufacture certain key components of our Products and our product candidates, as well as key components for future product candidates in clinical and preclinical testing in our research and development program.
−Removed: Although we entered into long-term commercial manufacturing agreements for the manufacture of our Products and our product candidates, and we have long-term agreements for the manufacture of our Biochronomer Technology, we might not be able to successfully negotiate long-term agreements with any additional third parties, or we might not receive all required regulatory approvals to utilize such third parties, and, accordingly, we might not be able to reduce or remove our dependence on a single supplier for the commercial manufacturing of our Products or our product candidates.
+Added: We do not own or operate manufacturing facilities for the production of commercial or clinical quantities of any product, including our Products.
+Added: Our ability to successfully commercialize our Products depends in part on our ability to arrange for, and rely on, other parties to manufacture our products at a competitive cost, in accordance with regulatory requirements, and in sufficient quantities for clinical testing and commercialization.
+Added: We currently rely on a small number of third-party manufacturers to produce compounds used in our Products.
+Added: Certain contract manufacturers are, at the present time (and are expected to be for the foreseeable future), our sole resource to manufacture certain key components of our Products.
+Added: Although we entered into long-term commercial manufacturing agreements for the manufacture of our Products, including long-term agreements for the manufacture of our Biochronomer Technology, we might not be able to successfully negotiate long-term agreements with any additional third parties, or we might not receive all required regulatory approvals to utilize such third parties, and, accordingly, we might not be able to reduce or remove our dependence on a single supplier for the commercial manufacturing of our Products.
We may have difficulties with these manufacturer relationships, and we may not be able to find replacement contract manufacturers on satisfactory terms or on a timely basis.
−Removed: At times, our contract manufacturers or other third parties might not perform their obligations under long-term commercial manufacturing agreements or other agreements, which could impede the manufacturing of our Products and our product candidates and could require us to incur additional costs, including legal fees, as we seek to enforce our contractual rights.
−Removed: Our reliance on third-party suppliers and contract manufacturers also subjects our business to risks associated with geographic areas in which those parties reside, which could include natural or man-made disasters, including epidemics, pandemics, acts of war or terrorism, or resource shortages.
+Added: At times, our contract manufacturers or other third parties might not perform their obligations under long-term commercial manufacturing agreements or other agreements, which could impede the manufacturing of our Products and could require us to incur additional costs, including legal fees, as we seek to enforce our contractual rights.
+Added: Our reliance on third-party suppliers and contract manufacturers also subjects our business to risks associated with geographic areas in which those parties reside, which could include natural or man-made disasters, including severe weather, epidemics, pandemics, acts of war or terrorism, armed conflict or resource shortages.
Due to regulatory and technical requirements, we may have limited ability to shift production to a different third-party should the need arise.
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In addition, such failure could be the basis for the FDA or foreign regulators to issue a warning or untitled letter or take other regulatory or legal action, including recall or seizure, total or partial suspension of production, suspension of ongoing clinical trials, refusal to approve pending applications or supplemental applications, and potentially civil and/or criminal penalties depending on the matter.
−Removed: Our Products and product candidates may be in competition with other products for access to the facilities of third parties and, consequently, could be subject to manufacturing delays if our contractors give other companies’ products greater priority than ours.
+Added: Our Products may be in competition with other products for access to the facilities of third parties and, consequently, could be subject to manufacturing delays if our contractors give other companies’ products greater priority than ours.
Additionally, our contractors might be required by government regulation or government authority to prioritize production of other products, such as priority-rated orders pursuant to the U.S.
Government Department of Defense Operation Warp Speed under the Health Resources Priority and Allocations System regulation.
−Removed: For this and other reasons, our third-party contract manufacturers may not be able to manufacture our Products or product candidates in a cost-effective or timely manner.
−Removed: If not manufactured in a timely manner, the clinical development of any of our Products or product candidates or their submission for regulatory approval could be delayed, and our ability to deliver products to market on a timely basis could be impaired.
+Added: For this and other reasons, our third-party contract manufacturers may not be able to manufacture our Products in a cost-effective or timely manner.
+Added: If not manufactured in a timely manner, the manufacture of any of our Products or their submission for regulatory approval could be delayed, and our ability to deliver products to market on a timely basis could be impaired.
This could increase our costs, cause us to lose revenue or market share and damage our reputation.
−Removed: Certain of the components used in the manufacture of our Products and product candidates are, or might be, sourced from a single vendor, and the loss or disruption of this vendor could significantly harm our business.
−Removed: Some of the critical materials and components used in manufacturing our Products and product candidates are, or might be, sourced from single suppliers.
+Added: 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.
+Added: 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.
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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.
−Removed: Our reliance on a single vendor for certain components used in the manufacturing of our Products and our product candidates 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 pandemics, acts of war or terrorism, armed conflict, geopolitical instability or resource shortages.
+Added: 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, geopolitical instability or resource shortages.
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.
−Removed: We continually evaluate our supply chains to identify potential risks and needs for additional manufacturers and other suppliers for the manufacturing of our Products and product candidates.
+Added: 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.
1 unchanged sentence
Any change in suppliers or the manufacturing process could require additional regulatory approval and result in operational delays.
−Removed: 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, rising geopolitical tensions, armed conflict or other factors, which could delay, prevent or impair our development or commercialization efforts.
−Removed: We obtain certain critical materials and components used in manufacturing our Products and our product candidates 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, 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.
+Added: 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.
+Added: 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).
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Similarly, the ongoing armed conflict between Russia and Ukraine remains unpredictable and could escalate into a broader armed conflict and additional economic sanctions by the U.S., the United Nations or other countries against Russia.
−Removed: If we are unable to obtain these critical materials and components in sufficient quantities and in a timely manner, the development, testing and clinical study of our Products and product candidates might be delayed or infeasible, and regulatory approval or commercialization of our Products and product candidates might be delayed, not obtained or hindered, which could significantly harm our business.
+Added: 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.
We have, or may have, significant inventory levels of drug products, and write-downs related to the impairment of those inventories may adversely impact or delay our profitability.
−Removed: We have, or may have, significant inventory levels of drug products, and we may increase those inventory levels as we continue to commercialize our Products and our product candidates.
+Added: We have, or may have, significant inventory levels of drug products, and we may increase those inventory levels as we continue to commercialize our Products.
We determine inventory levels of drug products based on a variety of estimates, including timing of regulatory approval of our drug products, market demand for our drug products and those of our competitors, entrance of competing drug products, introduction of new, or changes in interpretations of, pharmaceutical regulations, and changes in healthcare provider and insurer reimbursement policies.
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Given the time required to scale production and replenish inventory, our ability to correct for inaccurate estimates in a timely manner may be limited.
−Removed: Similarly, if we are unable to ramp up production of prospective product candidates to coincide with the regulatory approval of those product candidates, our ability to generate revenue and profits in the short term would be adversely impacted.
−Removed: If our competitors are able to meet demand with their products before we are able to produce and sell inventory, our ability to gain market share will be adversely impacted, which could materially and adversely affect our business, financial condition, cash flows and results of operations.
−Removed: In addition, if regulatory approval of any of our product candidates comes earlier than anticipated, as a result of preferential designations designed to hasten the approval process or otherwise, and we have not built up sufficient inventory to meet commercial demand, our ability to generate additional revenue sooner as a result of those early approvals may be diminished.
−Removed: We face intense competition from other companies developing products for the management of postoperative pain or the prevention of CINV and PONV.
−Removed: ZYNRELEF competes in the postoperative pain management market with MARCAINE TM (bupivacaine hydrochloride injection, solution, marketed by Pfizer Inc.) and generic forms of bupivacaine;
+Added: We face intense competition from other companies developing products for the management of postoperative pain or the prevention of CINV and PONV, which may limit our ability to sell our Products.
+Added: 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;
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AKYNZEO®(palonosetron, a 5-HT3 receptor antagonist, combined with netupitant, an NK1 receptor antagonist, marketed by Helsinn Therapeutics (U.S.), Inc.);
−Removed: VARUBI ® (rolapitant, marketed by TerSera Therapeutics LLC) and other products that include an NK 1 receptor antagonist that reach the market for the prevention of CINV.
+Added: 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.
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as KYTRIL) and palonosetron (formerly marketed by Eisai in conjunction with Helsinn Healthcare S.A.
+Added: 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.
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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.
−Removed: 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.
+Added: We will also face competition from these parties in 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.
−Removed: Our Products and product candidates may face competition from lower-cost generic products offered by our competitors.
+Added: Our Products may face competition from lower-cost generic products offered by our competitors, which may limit our ability to sell our Products or require us to reduce our pricing.
Pricing for therapeutics can be extremely competitive, and strict formulary guidelines enforced by payors may create significant challenges in the acceptance and profitability of branded products.
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It can be very difficult to predict the timing of the launch of generic products given the commonality of litigation with manufacturers over anticipated patent expiration.
−Removed: Our inability to accurately foresee and plan for generic product launches that may compete with our Products and our product candidates may significantly impact our potential revenues from such Products and product candidates.
−Removed: On the expiration or loss of patent protection for a branded product, or on the “at-risk” launch (despite pending patent infringement litigation against the generic product) by a manufacturer of a generic version of a drug that may compete with one of our products, we could quickly lose a significant portion of our sales of that Product or product candidate.
−Removed: The inability for a branded Product or product candidate we may sell to successfully compete against generic products could negatively impact sales of our Product or product candidate, reduce our ability to grow our business and significantly harm our business prospects.
−Removed: For example, generic versions of EMEND ® IV (fosaprepitant) launched in September 2019 following the expiration of the EMEND IV patents.
−Removed: As a result, we experienced increased competition for CINVANTI, which reduced CINVANTI sales and harmed and may continue to harm our business prospects.
−Removed: These and other risks related to the entry of generic product competing with CINVANTI are difficult to assess in terms of timing and impact on our operations and prospects.
−Removed: Additionally, while we had expected that generic versions of ALOXI (palonosetron) would launch in September 2018 following the expiration of the ALOXI patents, a U.S.
−Removed: Court of Appeals for the Federal Circuit decision in May 2017 ruled in favor of a generic drug company challenging the ALOXI patents, thereby potentially accelerating the entry of generic versions of ALOXI (palonosetron).
−Removed: The Supreme Court granted certiorari in June 2018 and affirmed the Federal Circuit decision in January 2019.
−Removed: As a result of this litigation, generic versions of ALOXI (palonosetron) have entered the market and we have experienced increased competition for SUSTOL, which has reduced SUSTOL sales and may continue to negatively affect our future business prospects.
−Removed: These and other risks related to the entry of generic product competing with SUSTOL are difficult to assess in terms of timing and impact on our operations and prospects.
+Added: Our inability to accurately foresee and plan for generic product launches that may compete with our Products may significantly impact our potential revenues from such Products.
+Added: On the expiration or loss of patent protection for a branded product, or on the “at-risk” launch (despite pending patent infringement litigation against the generic product) by a manufacturer of a generic version of a drug that may compete with one of our products, we could quickly lose a significant portion of our sales of that Product.
+Added: The inability for a branded Product we may sell to successfully compete against generic products could negatively impact sales of our Product, reduce our ability to grow our business and significantly harm our business prospects.
+Added: For example, we may face competition from newly developed generic products as the Hatch-Waxman Act seeks to stimulate competition by providing incentives to generic pharmaceutical manufacturers to introduce non-infringing forms of patented pharmaceutical products and to challenge patents on branded pharmaceutical products.
+Added: Currently, two companies are seeking approval via an Abbreviated New Drug Application (“ANDA”) in the United States for CINVANTI and one company is seeking approval via a 505(b)(2) application in the United States based on CINVANTI.
+Added: If the Company is unsuccessful in demonstrating infringement of its patents by an ANDA or 505(b)(2) product, or the validity of the Company’s patents is successfully challenged, cheaper ANDA or 505(b)(2) versions of our products may be launched commercially and may compete with CINVANTI, as they may be favored by insurers and third-party payors, which would significantly harm our business.
Our business and results of operations may suffer as a result of changes in our pricing or marketing strategies.
In an effort to remain competitive in the marketplace, we can determine, from time to time, to change our pricing or marketing strategies for our approved Products, including by altering the amount or availability of discounts or rebates for any of our approved Products.
−Removed: Any such changes could have short-term or long-term negative impacts on our revenues, which would cause our business and results of operations to suffer.
−Removed: For example, in October 2019, we eliminated the discounts on SUSTOL which reduced revenues.
+Added: Any such changes could have short-term or long-term negative impacts on
+Added: our revenues, which would cause our business and results of operations to suffer.
Price increases or changes to our marketing strategies may also negatively affect our reputation and our ability to secure and maintain reimbursement coverage for our approved Products, which could result in decreased demand and cause our business and results of operations to suffer.
Guidelines and recommendations published by various organizations could reduce the demand for or use of our Products.
−Removed: Government agencies promulgate regulations and guidelines directly applicable to us and to our Products and product candidates.
+Added: Government agencies promulgate regulations and guidelines directly applicable to us and to our Products.
In addition, professional societies, practice management groups, private health and science foundations and other organizations from time to time may publish papers, guidelines or recommendations to the healthcare and patient communities with respect to specific products or classes of products.
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Recommendations or guidelines that do not recognize a Product, suggest limitations or inadequacies of a Product or suggest the use of competitive or alternative products as the standard of care to be followed by patients and healthcare providers could result in decreased use or adoption of any of our Products which could have an adverse impact on our business, financial condition and results of operations.
+Added: Because the results of preclinical studies and clinical trials are not necessarily predictive of future results, we can provide no assurances that our Products or product candidates will have favorable results in future studies or receive regulatory approval or expansion of approved indications.
+Added: Positive results from preclinical studies or clinical trials should not be relied on as evidence that later or larger-scale studies will succeed.
+Added: Even if our Products or product candidates achieve positive results in early-stage preclinical studies or clinical studies, we will be required to demonstrate that they are safe and effective for use in Phase 3 studies before we can seek expanded indications or regulatory approvals for their commercial sale.
+Added: Even if our early-stage preclinical studies or clinical studies achieve the specified endpoints, the FDA may determine that these data are not sufficient to allow the commencement of Phase 3 studies.
+Added: There is an extremely high historical rate of failure of product candidates proceeding through clinical trials in our industry.
+Added: There is no guarantee that the efficacy of any of our product candidates shown in early patient studies will be replicated or maintained in future studies and/or larger patient populations.
+Added: Similarly, favorable safety and tolerability data seen in short-term studies might not be replicated in studies of longer duration and/or larger patient populations.
+Added: If any Product or product candidate demonstrates insufficient safety or efficacy in any preclinical study or clinical trial, we would experience potentially significant delays in, or be required to abandon, development of that Product for an expanded indication, or product candidate for approval.
+Added: In addition, product candidates in Phase 3 studies may fail to show the desired safety and efficacy despite having progressed through preclinical and earlier stage clinical trials, which could delay, limit or prevent regulatory approval.
+Added: Further, data obtained from pivotal clinical studies are susceptible to varying interpretations, which could delay, limit or prevent regulatory approval.
+Added: Regulatory approval may also be delayed, limited or prevented by other factors.
+Added: If we delay or abandon our efforts to develop any of our Products for expanded indications, or product candidates for approval, we may not be able to generate sufficient revenues to become profitable, and our reputation in the industry and in the investment community would likely be significantly damaged, each of which would cause our stock price to decrease significantly.
+Added: Interim, topline or preliminary data from our clinical trials that we announce or publish may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.
+Added: We may publicly disclose interim, topline, or preliminary data from our clinical trials, which is based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a full analysis of all data related to the particular trial.
+Added: We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity to fully and carefully evaluate all data.
+Added: As a result, the interim, topline, or preliminary results that we report may differ from future results of the same trials, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated.
+Added: Topline data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published.
+Added: As a result, topline data should be viewed with caution until the final data are available.
+Added: disclose interim data from our clinical trials.
+Added: Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available.
+Added: Adverse differences between interim, topline or preliminary data and final data could significantly harm our business prospects.
+Added: Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate or product and our business in general.
+Added: In addition, the information we choose to publicly disclose regarding a particular study or clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine is the material or otherwise appropriate information to include in our disclosure, and any information we determine not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise regarding a particular drug, product candidate or our business.
+Added: If the interim, topline, or preliminary data that we report differ from actual results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain expanded indications for our Products, or to obtain approvals for and commercialize our product candidates, our business, operating results, prospects or financial condition may be harmed.
+Added: Although the FDA might grant Fast Track, Breakthrough Therapy and Priority Review or similar designations to our Products and product candidates, there can be no assurance that any of our Products or product candidates that receive similar designations in the U.S.
+Added: or in any other regulatory jurisdictions will receive regulatory approval any sooner than other Products or product candidates that do not have such designations, or at all.
+Added: Fast Track designation is intended to facilitate the development and expedite the review of new therapies to treat serious conditions with unmet medical needs by providing sponsors with the opportunity for frequent interactions with the FDA.
+Added: Breakthrough Therapy designation is designed to expedite the development and review of drugs that are intended to treat serious conditions and for which preliminary clinical evidence indicates substantial improvement over available therapies on clinically significant endpoint(s).
+Added: Priority Review designation is for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment or prevention of serious conditions.
+Added: Product candidates that receive Fast Track or Breakthrough Therapy designation may receive more frequent interactions with the FDA regarding the product candidate’s development plan and clinical trials and may be eligible for the FDA’s Rolling Review and Priority Review.
+Added: Priority Review designation is intended to direct overall attention and resources of the FDA to the evaluation of such applications and means that the FDA’s goal is to take action on such applications within six months, compared to 10 months under standard review.
+Added: We can provide no assurances that any of our Products or product candidates that receive Fast Track, Breakthrough Therapy, Priority Review or similar designations in the U.S.
+Added: or in any other regulatory jurisdictions will receive regulatory approval any sooner than other Products or product candidates that do not have such designations, or at all.
+Added: The FDA or any foreign regulatory authorities may also withdraw or revoke Fast Track, Breakthrough Therapy, Priority Review or similar designations, or elect to treat designated candidates in a manner different from what was originally indicated, if they determine that any of our Products or product candidates that receive such designations no longer meet the relevant criteria.
+Added: Failure to realize the potential benefits of these designations could materially and adversely affect our business, financial condition, cash flows and results of operations.
+Added: Our product platforms or product development efforts may not produce safe, efficacious or commercially viable products, and, if we are unable to develop new products, our business may suffer.
+Added: Our long-term viability and growth will depend on the successful development of products through our research and development activities.
+Added: Product development is very expensive and involves a high degree of risk.
+Added: Only a small number of research and development programs result in the commercialization of a product.
+Added: Success in preclinical work or early-stage clinical trials does not ensure that later-stage or larger-scale clinical trials will be successful.
+Added: Our ability to complete our clinical trials in a timely fashion depends in large part on a number of key factors, including protocol design, regulatory and IRB approval, the rate of patient enrollment in clinical trials and compliance with extensive cGCP.
+Added: In addition, because we fund the development of our Products and product candidates, we may not be able to continue to fund all such development efforts to completion or to provide the support necessary to perform the
+Added: clinical trials, obtain regulatory approvals, or market any approved products.
+Added: If our drug delivery technologies or product development efforts fail to result in the successful development and commercialization of our Products and product candidates, or if our new Products do not perform as anticipated, such events could materially and adversely affect our business, financial condition, cash flows and results of operations.
+Added: We rely on third parties to conduct our preclinical testing and conduct our clinical trials, and their failure to perform their obligations in a timely and competent manner may delay development and commercialization of our Products and product candidates and our business could be substantially harmed.
+Added: We have used contract research organizations (“CROs”) to oversee or provide selected services for our clinical trials for our Products and our product candidates, and we expect to use the same or similar organizations for our future clinical trials and pipeline programs.
+Added: There can be no assurance that these CROs will perform their obligations at all times in a competent or timely fashion, and we must rigorously oversee their activities in order to be confident in their conduct of these trials on our behalf.
+Added: If the CROs fail to commit resources to our Products or product candidates, our clinical programs could be delayed, terminated or unsuccessful, and we may not be able to obtain initial or expanded regulatory approvals for, or successfully commercialize, them.
+Added: Different cultural and operational issues in foreign countries could cause delays or unexpected problems with patient enrollment or with the data obtained from those locations.
+Added: If we experience significant delays in the progress of our clinical trials or experience doubts with respect to the quality of data derived from our clinical trials, we could face significant delays in gaining necessary product approvals.
+Added: We also rely on third parties to assist in conducting our preclinical studies in accordance with GLP and the Animal Welfare Act requirements.
+Added: We, our CROs and other third parties are required to comply with cGCP, which are regulations and guidelines enforced by the FDA, the Competent Authorities of the Member States of the EEA and comparable foreign regulatory authorities.
+Added: Regulatory authorities enforce cGCP through periodic inspections of trial sponsors, principal investigators and trial sites.
+Added: If we or any of our CROs fail to comply with applicable cGCP, the clinical data generated in the clinical trials may be deemed unreliable, and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications.
+Added: We cannot be certain that on inspection by a given regulatory authority, such regulatory authority will determine that any of our ongoing or future clinical trials comply with cGCP.
+Added: In addition, all of our clinical trials must be conducted with product produced under cGMP.
+Added: Failure to comply with these regulations may require us to repeat preclinical and clinical trials, which would increase our related expenses and delay the regulatory approval process.
+Added: Our CROs and other third parties we may engage to support our development programs are not our employees, and, except for remedies available to us under our agreements with such CROs, we cannot control whether or not they devote sufficient time and resources to our ongoing clinical, non-clinical and preclinical programs.
+Added: Outsourcing these functions involves risk that third parties may not perform to our standards, may not produce results in a timely manner, or may fail to perform at all.
+Added: If CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines or if the quality or accuracy of the preclinical results or clinical data they obtain is compromised due to the failure to adhere to test requirements, our clinical protocols, regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our Products and product candidates.
+Added: As a result, our results of operations and the commercial prospects for our Products and product candidates would be harmed, our costs could increase and our ability to generate revenues could be delayed.
If we are unable to recruit and retain skilled employees, we may not be able to achieve our objectives.
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If we lose key members of our senior management team, we may not be able to find suitable replacements and our business may be harmed as a result.
−Removed: This competitive situation became exacerbated by the increase in employee resignations that took place throughout the U.S., in part as a result of the COVID-19 pandemic, which was commonly referred to as the “great resignation.” In addition, our ability to recruit and retain key skilled employees may be hampered by our recently announced workforce reduction.
−Removed: If we fail to adequately address any of the issues referred to above, it could adversely impact our ability to recruit and retain our skilled employees which may result in a material adverse effect on our business, operating results and financial condition.
−Removed: We may not realize the expected benefits of our cost-saving initiatives.
−Removed: In June 2023, in connection with our efforts to decrease costs and maintain a streamlined organization to support our acute care and oncology care franchises, we implemented a workforce reduction that resulted in the termination of approximately 25% of our workforce.
−Removed: If we experience excessive unanticipated inefficiencies or incremental costs in connection with restructuring activities, such as unanticipated inefficiencies caused by our reduced headcount, we may be unable to meaningfully realize cost savings or capitalize on future opportunities and we may incur expenses
−Removed: in excess of what we anticipate.
−Removed: Any of these outcomes could prevent us from meeting our strategic objectives and could adversely impact our results of operations and financial condition.
+Added: If we fail to adequately address any of the issues referred to above, it could
+Added: adversely impact our ability to recruit and retain our skilled employees which may result in a material adverse effect on our business, operating results and financial condition.
Our business strategy may include acquisitions of other businesses, products or product licenses.
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We may not be able to enter into collaborative agreements or may not be able to negotiate commercially acceptable terms for these agreements.
−Removed: Our business strategy may include the entry into collaborative agreements for the development and commercialization of our Products and our product candidates.
+Added: Our business strategy may include the entry into collaborative agreements for the development and commercialization of our Products.
The negotiation and consummation of these types of agreements typically involve simultaneous discussions with multiple potential collaborators and require significant time and resources from our officers, business development and research and development staff.
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If we fail to establish and maintain necessary collaborative relationships, our business prospects could suffer.
−Removed: Natural or man-made disasters, including epidemics, pandemics, acts of war or terrorism, or resource shortages, could disrupt our investigational drug candidate development and approved drug commercialization efforts or have other negative consequences on our business and adversely affect results.
−Removed: Our ongoing or planned clinical studies and approved drug commercialization efforts could be delayed or disrupted indefinitely on the occurrence of a natural or man-made disaster, including an epidemic, pandemic, or other disease outbreak, cyberattack, or acts of war or terrorism, or resource shortages.
−Removed: For example, COVID-19 caused a decline in, and suspensions of, elective surgeries, which negatively impacted our ability to conduct our clinical trials.
−Removed: In addition, COVID-19 slowed the diagnosis procedures to identify cancer and reduced the number of new cancer patients seeking treatment which may negatively impact our CINV products.
+Added: Natural or man-made disasters, including severe weather, epidemics, pandemics, cyber attacks, acts of war or terrorism, armed conflict, federal workforce uncertainty, or resource shortages, could disrupt our investigational drug candidate development and approved drug commercialization efforts or have other negative consequences on our business and adversely affect results.
+Added: Our ongoing or planned clinical studies and approved drug commercialization efforts could be delayed or disrupted indefinitely on the occurrence of a natural or man-made disaster, including severe weather, an epidemic, a pandemic, or other disease outbreak, cyberattacks, acts of war or terrorism, armed conflict, or resource shortages.
We are also vulnerable to damage from other disasters, such as power losses, fires, earthquakes, floods, hurricanes and similar events.
−Removed: For example, a natural or man-made disaster, including an epidemic, pandemic, or other disease outbreak, cyberattack, or act of war or terrorism, and the resulting damage could negatively impact enrollment and participation in our clinical studies, divert attention and resources at our research sites, cause unanticipated delays in the collection and receipt of data from our clinical studies, cause unanticipated delays in communications with, and any required approvals from, the FDA, European Medicines Agency, United Kingdom’s Medicines and Healthcare Products Regulatory Agency, Health Canada, and other regulatory authorities, and cause unanticipated delays in the manufacturing and distribution of our Products and our product candidates.
+Added: Any such natural or man-made disaster, including severe weather, an epidemic, a pandemic, or other disease outbreak, cyberattacks, acts of war or terrorism, armed conflict, and the resulting damage could negatively impact enrollment and participation in our clinical studies, divert attention and resources at our research sites, cause unanticipated delays in the collection and receipt of data from our clinical studies, cause unanticipated delays in communications with, and any required approvals from, the FDA, European Medicines Agency, United Kingdom’s Medicines and Healthcare Products Regulatory Agency, Health Canada, and other regulatory authorities, and cause unanticipated delays in the manufacturing and distribution of our Products.
If a significant disaster occurs, our ability to continue our operations could be seriously impaired and we may not have adequate insurance to cover any resulting losses.
Any significant unrecoverable losses could seriously impair our operations and financial condition.
−Removed: Further, the current Russia-Ukraine conflict has created extreme volatility in the global financial markets and is expected to have further global economic consequences, including continued disruptions of the global supply chain and energy markets and heightened volatility of commodity prices.
−Removed: government and other nations have imposed significant restrictions on most companies’ ability to do business in Russia as a result of the conflict, and it is not possible to predict the broader or longer-term consequences of this conflict, which could include further sanctions, embargoes, regional instability, geopolitical shifts and adverse effects on macroeconomic conditions, security conditions, currency exchange rates and financial markets.
+Added: Further, the recent geo-political conflicts have created extreme volatility in the global financial markets and are expected to have further global economic consequences, including continued disruptions of the global supply chain and energy markets and heightened volatility of commodity prices.
Any such instability or disruption may have adverse consequences on us or the third parties on whom we rely, including as a result of a general downturn in global economic conditions, deterioration in the credit or equity markets, or more direct impacts on operational matters.
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Our potential international expansion of our business may expose us to new business, regulatory, political, operational, financial and economic risks associated with such expansion and could adversely affect our business, financial condition, results of operations and growth.
−Removed: If our Products or product candidates are marketed internationally by us or a potential third-party partners, we and such third-party partners could be subject to additional risks related to operating in foreign countries, including:
+Added: If our Products are marketed internationally by us or a potential third-party partners, we and such third-party partners could be subject to additional risks related to operating in foreign countries, including:
• general economic conditions and monetary and fiscal policy, including economic weakness or inflation;
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• production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad, if applicable;
−Removed: • logistical challenges resulting from distributing our Products and product candidates to foreign countries;
+Added: • logistical challenges resulting from distributing our Products to foreign countries;
• economic or business interruptions resulting from civil unrest or social, political, economic, or diplomatic developments, including geo-political actions, such as armed conflict or terrorism.
−Removed: These and other risks associated with international operations may compromise our ability to earn revenue from arrangements with potential third-party partners for our Products or product candidates and, therefore, could adversely affect our business, operations and planned international expansion.
+Added: These and other risks associated with international operations may compromise our ability to earn revenue from arrangements with potential third-party partners for our Products and, therefore, could adversely affect our business, operations and planned international expansion.
Risks Related to Our Financial Condition
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• the commercial success of our Products;
−Removed: • the time and expense required to pursue FDA and/or non-U.S.
−Removed: regulatory approvals for our product candidates, whether such approvals are obtained and the scope of any approved product label;
• the cost of possible acquisitions of technologies, compounds, product rights or companies;
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• the time and expense required to prosecute, enforce and/or challenge patent and other intellectual property rights;
−Removed: • the costs of potential litigation; and
+Added: • the costs and impacts of current and potential future litigation; and
• the costs associated with recruiting and compensating a highly skilled workforce in an environment where competition for such employees may be intense.
−Removed: To achieve and sustain profitability, we must, alone or in cooperation with others, successfully develop, obtain regulatory approval for, manufacture, market and sell our Products, including our current work commercializing our Products and our anticipated work commercializing our product candidates.
−Removed: We have incurred substantial expenses in our efforts to develop and commercialize our Products and our product candidates and we may never generate sufficient revenue to become profitable or to sustain profitability.
−Removed: Additional capital may be needed in the future to enable us to implement our business plan, and we may be unable to raise capital, which would force us to limit or cease our operations and related product development programs.
−Removed: As of December 31, 2023, we had cash, cash equivalents and short-term investments of $80.4 million.
−Removed: Historically, we have financed our operations, including technology and product research and development, primarily through sales of our common stock and debt financings.
+Added: To achieve and sustain profitability, we must, alone or in cooperation with others, successfully develop, obtain regulatory approval for, manufacture, market and sell our Products, including our current work commercializing our Products .
+Added: We have incurred substantial expenses in our efforts to develop and commercialize our Products and we may never generate sufficient revenue to become profitable or to sustain profitability.
+Added: Additional capital will be needed in the future to enable us to implement our business plan, and we may be unable to raise capital, which would force us to limit or cease our operations.
+Added: As of December 31, 2024, we had cash, cash equivalents and short-term investments of $59.3 million and indebtedness under our Senior Convertible Notes and Working Capital Facility totaling $175.5 million.
+Added: We expect that we will need to refinance, or otherwise satisfy, our current indebtedness of $175.5 million to fully fund our current business plan and meet all of our commitments.
+Added: Historically, we have financed our operations, including technology and product research and development, primarily through sales of our common stock, product sales and debt financings.
Our capital requirements and liquidity going forward will depend on numerous factors, including but not limited to:
−Removed: the costs associated with the U.S.
−Removed: commercial launches of ZYNRELEF and APONVIE.;
• the degree of commercial success of our Products and our product candidates, if approved;
• the timing and cost to manufacture our Products and our product candidates;
−Removed: the number and characteristics of product development programs we pursue and the pace of each program, including the timing of clinical trials;
−Removed: the time, cost and outcome involved in seeking other regulatory approvals;
−Removed: scientific progress in our research and development programs;
• the magnitude and scope of our research and development programs;
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• the impact of competitive products;
−Removed: the cost and timing of establishing sales, marketing and distribution capabilities if we commercialize products independently;
−Removed: the cost of establishing clinical and commercial supplies of our product candidates;
−Removed: the impact of our restructuring plans;
−Removed: and general market conditions.
−Removed: Management’s view of our liquidity relies on estimates and assumptions about the market opportunity for the recently expanded U.S.
−Removed: label of ZYNRELEF, which estimates and assumptions are subject to significant uncertainty.
−Removed: We may not be able to raise additional capital when needed or desired, or we may need to raise additional capital on unfavorable terms, which could result in dilution to existing stockholders.
−Removed: We may not be able to raise sufficient additional capital when needed on favorable terms, or at all.
−Removed: If we are unable to obtain adequate funds, we may be required to curtail significantly or cease our operations.
−Removed: The timing and degree of any future capital requirements will depend on many factors, including:
−Removed: • our ability to successfully commercialize, market and achieve market acceptance of our Products and our product candidates;
−Removed: • the status of regulatory approval of any pending applications with the FDA, or other regulators, as the case may be, and the costs involved with pursuing regulatory approvals;
−Removed: • the number and characteristics of product development programs we pursue and the pace of each program;
−Removed: • the scope, rate of progress, results and costs of preclinical testing and clinical trials;
−Removed: • our ability to establish and maintain strategic collaborations or partnerships for research, development, clinical testing, manufacturing and marketing of our product candidates;
+Added: • the cost of establishing supply arrangements for our Products;
• the cost and timing of establishing or enlarging sales and marketing capabilities;
−Removed: • the cost of establishing supply arrangements for clinical and commercial development of our Products and our product candidates;
−Removed: • the unanticipated delays due to manufacturing difficulties, supply constraints or changes in the regulatory environment, including as a result of geopolitical uncertainty, or other factors (including the current Russia-Ukraine conflict).
+Added: • the unanticipated delays due to manufacturing difficulties, supply constraints or changes in the regulatory environment, including as a result of geopolitical uncertainty, or other factors;
+Added: • the impact of the $150.0 million in aggregate principal amount of the Senior Convertible Notes (as defined below) that are outstanding and will mature on May 26, 2026, unless earlier converted, redeemed or repurchased;
+Added: • the impact of the $25.5 million in aggregate principal amount of the Working Capital Facility (as defined below) that is outstanding and will mature on the earlier of earlier of (a) September 1, 2027 and (b) to the extent that any of the Senior Convertible Notes remain outstanding on such date, (i) May 12, 2026 or (ii) in the event that the maturity date of any of the Senior Convertible Notes is extended, prior to May 12, 2026, to August 11, 2026 or later, the date that is ninety-one days prior to the maturity date of such further extended Senior Convertible Notes;
+Added: • general market conditions.
If we issue additional equity securities or securities convertible into equity securities to raise funds, our stockholders will suffer dilution of their investment, and such issuance may adversely affect the market price of our common stock.
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These restrictive covenants may include, among other things, limitations on borrowing and specific restrictions on the use of our assets, as well as prohibitions on our ability to create liens, pay dividends, redeem capital stock or make investments.
−Removed: For example, under a working capital facility agreement we entered into with Hercules Capital, Inc.
−Removed: and several banks and other financial institutions, we are required to hold cash of no less than $8.5 million, if our market capitalization is less than $400 million.
+Added: For example, under a working capital facility agreement that we entered into with Hercules Capital, Inc.
+Added: as administrative agent and collateral agent, and the lenders party thereto (the "Working Capital Facility Agreement" and the facility thereunder, the "Working Capital Facility"), we are required to hold cash of no less than $8.5 million, if our market capitalization is less than $400 million.
The Working Capital Facility Agreement also contains customary representations and warranties and customary affirmative and negative covenants, including, among other things, restrictions on indebtedness, liens, investments, mergers, dispositions, prepayment of other indebtedness, and dividends and other distributions, subject to certain exceptions.
−Removed: Our Senior Unsecured Convertible Notes also impose certain negative covenants on the Company, including on the incurrence of certain indebtedness, the creation of certain liens and selling royalty interests in Company assets.
+Added: Our outstanding senior unsecured convertible notes due 2026, (the "Senior Convertible Notes") also impose certain negative covenants on the Company, including on the incurrence of certain indebtedness, the creation of certain liens and selling royalty interests in Company assets.
In the event that additional funds are obtained through arrangements with collaborative partners, these arrangements may require us to relinquish rights to some of our technologies, product candidates or Products on terms that are not favorable to us or require us to enter into a collaboration arrangement that we would otherwise seek to develop and commercialize ourselves.
If adequate funds are not available, we may default on our indebtedness, be required to further delay, reduce the scope of, or eliminate one or more of our product development programs and reduce personnel-related and other costs, which would have a negative impact on our business.
+Added: Management’s view of our liquidity relies on estimates and assumptions about the market opportunity for our Products, which estimates and assumptions are subject to significant uncertainty.
Provisions contained in our debt instruments limit our ability to incur additional indebtedness.
−Removed: The terms of our Senior Unsecured Convertible Notes require us to seek approval from the holders of such notes before taking certain actions, including incurring certain additional indebtedness, modifying the terms of certain existing indebtedness, creating liens or selling royalty interests in Company assets.
−Removed: The Senior Unsecured Convertible Notes also contain provisions that trigger events of default on any default of our financial obligations under certain material contracts we may enter into.
+Added: The terms of our Senior Convertible Notes require us to seek approval from the holders of such notes before taking certain actions, including incurring certain additional indebtedness, modifying the terms of certain existing indebtedness, creating liens or selling royalty interests in Company assets.
+Added: Our Senior Convertible Notes also contain provisions that trigger events of default on any default of our financial obligations under certain material contracts we may enter into.
As a result, we may not be able to raise funds through the issuance of debt or selling of royalty interests in the future, which could impair our ability to finance our business obligations or pursue business expansion initiatives.
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The administration of drugs in humans, whether in clinical studies or commercially, carries the inherent risk of product liability claims whether or not the drugs are actually the cause of an injury.
−Removed: Our Products, our product candidates and other products that we may commercially market in the future may cause, or may appear to have caused, injury or dangerous drug reactions, and we may not learn about or understand those effects until the Product or product candidate has been administered to patients for a prolonged period of time.
+Added: Our Products and other products that we may commercially market in the future may cause, or may appear to have caused, injury or dangerous drug reactions, and we may not learn about or understand those effects until the Product has been administered to patients for a prolonged period of time.
Although we are insured against such risks up to an annual aggregate limit in connection with clinical trials and commercial sales of our Products, our present product liability insurance may be inadequate and may not fully cover the costs of any claim or any ultimate damages we might be required to pay.
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Tax or other regulatory authorities may challenge our characterization of services providers as independent contractors both under existing laws and regulations and under laws and regulations adopted in the future.
−Removed: We are aware of a number of judicial decisions and legislative proposals that could bring about major changes in the way workers are classified, including the California legislature’s passage of California Assembly Bill 5, which California Governor Gavin Newsom signed into law in September 2019 (“AB 5”) and Assembly Bill 2257, which went into effect in September 2020 and amended certain portions of AB 5 (“AB 2257”).
−Removed: AB 5 and AB 2257 are often referred to collectively simply as AB 5.
−Removed: AB 5 purports to codify the holding of the California Supreme Court’s unanimous decision in Dynamex Operations West, Inc.
−Removed: Superior Court of Los Angeles, which introduced a new test for determining worker classification that is widely viewed as expanding the scope of employee relationships and narrowing the scope of independent contractor relationships.
−Removed: While AB 5 exempts certain licensed health care professionals, including physicians and psychologists, not all of our independent contractors work in exempt occupations.
−Removed: Given AB 5’s relatively recent passage, there is little guidance from the regulatory authorities charged with its enforcement and there is a significant degree of uncertainty regarding its application.
−Removed: In addition, AB 5 has been the subject of widespread national discussion and it is possible that other jurisdictions might enact similar laws.
+Added: We are aware of a number of judicial decisions and legislative proposals that could bring about major reforms in worker classification, including the California legislature’s 2019 passage of California Assembly Bill 5 (“AB 5”).
+Added: AB 5 purports to codify a new test for determining worker classification that is widely viewed as expanding the scope of employee relationships and narrowing the scope of independent contractor relationships.
+Added: There is limited guidance from the regulatory authorities charged with its enforcement, and there is a significant degree of uncertainty regarding its application.
+Added: In addition, AB 5 has been the subject of widespread national discussion and it is possible that other jurisdictions, including New York, may enact similar laws.
As a result, there is significant uncertainty regarding what the state, federal and foreign worker classification regulatory landscape will look like in future years.
The current economic climate indicates that the debate over worker classification will continue for the foreseeable future.
−Removed: If such regulatory authorities or state, federal or foreign courts were to determine that our services providers are employees
−Removed: and not independent contractors, we would, among other things, be required to withhold income taxes, to withhold and pay Social Security, Medicare and similar taxes, to pay unemployment and other related payroll taxes, and to provide certain employee benefits.
+Added: If such regulatory authorities or state, federal or foreign courts were to determine that our services providers are employees and not independent contractors, we would, among other things, be required to withhold income taxes, to withhold and pay Social Security, Medicare and similar taxes, to pay unemployment and other related payroll taxes, and to provide certain employee benefits.
We could also be liable for unpaid past taxes and other costs and subject to penalties.
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Actual events involving limited liquidity, defaults, non-performance or other adverse developments that affect financial institutions, transactional counterparties or other companies in the financial services industry or the financial services industry generally, or concerns or rumors about any events of these kinds or other similar risks, have in the past and may in the future lead to market-wide liquidity problems.
−Removed: For example, on March 10, 2023, Silicon Valley Bank (“SVB”), was closed by the California Department of Financial Protection and Innovation, which appointed the Federal Deposit Insurance Corporation, or the FDIC, as receiver.
−Removed: Similarly, on March 12, 2023, Signature Bank and Silvergate Capital Corp.
−Removed: were each swept into receivership.
−Removed: Although a statement by the Department of the Treasury, the Federal Reserve and the FDIC stated that all depositors of SVB would have access to all of their money after only one business day of closure, including funds held in uninsured deposit accounts, borrowers under credit agreements, letters of credit and certain other financial instruments with SVB, Signature Bank or any other financial institution that is placed into receivership by the FDIC may be unable to access undrawn amounts thereunder.
If any of our counterparties to any such instruments were to be placed into receivership, we may be unable to access such funds.
In addition, if any parties with whom we conduct business are unable to access funds pursuant to such instruments or lending arrangements with such a financial institution, such parties’ ability to pay their obligations to us or to enter into new commercial arrangements requiring additional payments to us could be adversely affected.
−Removed: In this regard, counterparties to SVB credit agreements and arrangements, and third parties such as beneficiaries of letters of credit (among others), may experience direct impacts from the closure of SVB and uncertainty remains over liquidity concerns in the broader financial services industry.
−Removed: As of March 10, 2023, we maintained a de minimis amount of cash and cash equivalents, in the low single digit millions of U.S.
−Removed: dollars, with SVB, all of which we were able to successfully recover.
Although we assess our banking relationships as we believe necessary or appropriate, our access to funding sources and other credit arrangements in amounts adequate to finance or capitalize our current and projected future business operations could be significantly impaired by factors that affect us, the financial institutions with which we have arrangements directly, or the financial services industry or economy in general.
These factors could include, among others, events such as liquidity constraints or failures, the ability to perform obligations under various types of financial, credit or liquidity agreements or arrangements, disruptions or instability in the financial services industry or financial markets, or concerns or negative expectations about the prospects for companies in the financial services industry.
−Removed: These factors could involve financial institutions or financial services industry companies with which we have financial or business relationships, but could also include factors involving financial markets or the financial services industry generally.
+Added: These factors could involve financial institutions or financial services industry companies with which we have financial or business relationships, but could also include factors involving financial markets or the financial
+Added: services industry generally.
The results of events or concerns that involve one or more of these factors could include a variety of material and adverse impacts on our current and projected business operations and our financial condition and results of operations.
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Any of these impacts, or any other impacts resulting from the factors described above or other related or similar factors not described above, could have material adverse impacts on our liquidity and our current and/or projected business operations and financial condition and results of operations.
−Removed: Further, any further deterioration in the macroeconomic economy or financial services industry could lead to losses or defaults by parties with whom we conduct business, which in turn, could have a material adverse effect on our current and/or projected business operations and results of operations and financial condition.
+Added: Further, any additional deterioration in the macroeconomic economy or financial services industry could lead to losses or defaults by parties with whom we conduct business, which in turn, could have a material adverse effect on our current and/or projected business operations and results of operations and financial condition.
For example, a party with whom we conduct business may fail to make payments when due, default under their agreements with us, become insolvent or declare bankruptcy.
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Risks Related to Our Industry
−Removed: Drug development involves a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results.
−Removed: Conducting clinical trials is a lengthy, time-consuming and expensive process.
−Removed: For example, we incurred significant expenses in developing our Products, with no guarantees that doing so would result in a commercially viable product.
−Removed: Before obtaining regulatory approvals for the commercial sale of any products, we, or our potential partners, must demonstrate through preclinical testing and clinical trials that our product candidates are safe and effective for their intended uses in humans.
−Removed: We have incurred and will continue to incur substantial expense and devote a significant amount of time to preclinical testing and clinical trials.
−Removed: The outcome of clinical testing is inherently uncertain.
−Removed: Failure can occur at any time during the clinical trial process.
−Removed: The results of preclinical studies and early clinical trials of product candidates may not be predictive of the results of later-stage clinical trials.
−Removed: In addition, regulations are not static, and regulatory agencies, including the FDA, alter their staff, interpretations and practices and may in the future impose more stringent requirements than are currently in effect, which may adversely affect our planned drug development and/or our commercialization efforts.
−Removed: Satisfying regulatory requirements typically takes a significant number of years and can vary substantially based on the type, complexity and novelty of the product candidate.
−Removed: Our business, results of operations and financial condition could be materially and adversely affected by any delays in, or termination of, our clinical trials.
−Removed: Factors that could impede our ability to generate commercially viable products through the conduct of clinical trials include:
−Removed: • insufficient funds to conduct clinical trials;
−Removed: • the inability to find partners, if necessary, for support, including research, development, manufacturing or clinical needs;
−Removed: • the failure of tests or studies necessary to submit an NDA, such as clinical studies, bioequivalence studies in support of a 505(b)(2) regulatory filing, or stability studies;
−Removed: • the failure of clinical trials to demonstrate the safety and efficacy of our product candidates to the extent necessary to obtain regulatory approvals;
−Removed: • the failure by us or third-party investigators, CROs, or other third parties involved in the research to adhere to regulatory requirements applicable to the conduct of clinical trials;
−Removed: • the failure of preclinical testing and early clinical trials to predict results of later clinical trials;
−Removed: • any delay in completion of clinical trials caused by a regional, national or global disturbance where we or our collaborative partners are enrolling patients in clinical studies, such as a pandemic (including COVID-19), terrorist activities, cyberattack, or war, political unrest, a natural or man-made disaster or any other reason or event, resulting in increased costs;
−Removed: • any delay in obtaining advice from the FDA or similar regulatory authorities;
−Removed: • the inability to obtain regulatory approval of our product candidates following completion of clinical trials, or delays in obtaining such approvals.
−Removed: From time to time, even if a product candidate has not failed, we may voluntarily determine to pause development, which effectively halts our ability to commercialize the product.
−Removed: For example, we recently decided to pause the development of HTX-034 to evaluate the program and market potential going forward.
−Removed: There can be no assurance that our decisions with respect to such pauses, and subsequent resumptions, if any, will yield the most favorable result for the Company.
−Removed: There can be no assurance that if our clinical trials are successfully initiated and completed we will be able to obtain approval by the FDA in the U.S.
−Removed: or similar regulatory authorities elsewhere in the world in a timely manner, if at all.
−Removed: If we fail to successfully develop and commercialize one or more of our product candidates, we may be unable to generate sufficient revenues to attain profitability, and our reputation in the industry and in the investment community would likely be significantly damaged, each of which would cause our stock price to significantly decrease.
−Removed: Delays in, or suspensions and terminations of, clinical testing could increase our costs and delay our ability to obtain regulatory approval for, and commercialize, our product candidates.
−Removed: Before we can receive regulatory approval for the commercial sale of our product candidates, the FDA and comparable authorities in non-U.S.
−Removed: jurisdictions require extensive preclinical safety testing and clinical trials to demonstrate their safety and efficacy.
−Removed: Significant delays in preclinical and clinical testing could materially impact our product development costs and delay regulatory approval of our product candidates.
−Removed: Our ability to complete clinical trials in a timely manner, or at all, has in the past been, and could in the future be impacted by, among other factors:
−Removed: • delay or failure in reaching agreement with the FDA or comparable foreign regulatory authority on a trial design that we are able to execute;
−Removed: • delay or failure in obtaining authorization to commence a trial or inability to comply with conditions imposed by a regulatory authority regarding the scope or design of a clinical study;
−Removed: • delay or failure in reaching agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;
−Removed: • delay or failure in obtaining IRB approval or the approval of other reviewing entities, including comparable foreign entities, to conduct a clinical trial at each site;
−Removed: • withdrawal of clinical trial sites from our clinical trials as a result of changing standards of care or the ineligibility of a site to participate in our clinical trials;
−Removed: • delay or failure in obtaining clinical materials;
−Removed: • delay or failure in recruiting and enrolling suitable subjects to participate in a trial;
−Removed: • delay or failure of subjects completing a trial or returning for post-treatment follow-up;
−Removed: • clinical sites and investigators deviating from trial protocol, failing to conduct the trial in accordance with regulatory requirements, or dropping out of a trial;
−Removed: • inability to identify and maintain a sufficient number of trial sites, many of which may already be engaged in other clinical trial programs, including some that may be for the same indication;
−Removed: • failure of our third-party clinical trial managers to satisfy their contractual duties or meet expected deadlines;
−Removed: • delay or failure in adding new clinical trial sites;
−Removed: • ambiguous or negative interim results or results that are inconsistent with earlier results;
−Removed: • feedback from the FDA, the IRB, data safety monitoring boards or comparable foreign entities, or results from earlier stage or concurrent preclinical and clinical studies that might require modification to the protocol;
−Removed: • decisions by the FDA, the IRB, comparable foreign regulatory entities, or recommendations by a data safety monitoring board or comparable foreign regulatory entity to suspend or terminate clinical trials at any time for safety issues or for any other reason;
−Removed: • unacceptable risk-benefit profiles or unforeseen safety issues or adverse side effects;
−Removed: • failure to demonstrate a benefit from using a drug;
−Removed: • manufacturing issues, including problems with manufacturing or obtaining from third parties sufficient quantities of a product candidate for use in clinical trials;
−Removed: • changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
−Removed: We rely on CROs and clinical trial sites to ensure the proper and timely conduct of our clinical trials and while we have agreements governing their activities, we have limited influence over CROs’ actual performance.
−Removed: Our failure to successfully establish, recruit for, and oversee our clinical trials could delay our product development efforts and negatively impact our business.
−Removed: If we experience delays in the completion of any ongoing study, the commercial prospects of our product candidates or any of our other future product candidates could be harmed, and our ability to generate product revenue will be delayed.
−Removed: Any delays in completing our clinical trials will increase our costs, slow our product candidates’ development and approval process and jeopardize our ability to commence product sales and generate revenues.
−Removed: Any of these occurrences may harm our business, financial condition and prospects significantly.
−Removed: We may not obtain regulatory approval for our product candidates in development.
−Removed: Regulatory approval may also be delayed or revoked or may impose limitations on the indicated uses of a product candidate.
−Removed: If we are unable to obtain regulatory approval for our product candidates in development, our business will be substantially harmed.
−Removed: The process for obtaining regulatory approval of a new drug is time-consuming, is subject to unanticipated delays and costs and requires the commitment of substantial resources.
−Removed: Any product that we or our potential future collaborative partners develop must receive all necessary regulatory agency approvals or clearances before it may be marketed in the U.S.
−Removed: or other countries.
−Removed: Human pharmaceutical products are subject to rigorous preclinical and clinical testing and other requirements by the FDA in the U.S.
−Removed: and similar health authorities in foreign countries.
−Removed: We may not receive necessary regulatory approvals or clearances to market our product candidates currently in development in the U.S.
−Removed: or in other jurisdictions, as a result of changes in regulatory policies prior to approval or other events.
−Removed: Additionally, data obtained from preclinical and clinical activities, or from stability or bioequivalence studies, are susceptible to varying interpretations that could delay, limit or prevent regulatory agency approvals or clearances.
−Removed: Our product candidates could fail to receive regulatory approval from the FDA or a comparable foreign regulatory authority for many reasons, including:
−Removed: • disagreement with the design or implementation of our clinical trials;
−Removed: • failure to demonstrate that the product candidate is safe and effective for its proposed indication;
−Removed: • failure of clinical trial results to meet the level of statistical significance required for approval;
−Removed: • the failure of third parties to manage and conduct the trials or perform necessary oversight to meet expected deadlines or to comply with regulatory requirements;
−Removed: • failure to demonstrate that the product candidate’s clinical and other benefits outweigh its safety risks;
−Removed: • disagreement with our interpretation of data from preclinical studies or clinical trials;
−Removed: • the insufficiency of data collected from clinical trials to support the submission and filing of an NDA or other submission or to obtain regulatory approval;
−Removed: • disapproval of the manufacturing processes or facilities of third-party manufacturers with whom we contract for clinical and commercial supplies;
−Removed: • changes in approval policies or regulations that render our preclinical and clinical data insufficient for approval.
−Removed: The FDA or a comparable non-U.S.
−Removed: regulatory authority may require additional preclinical or clinical data to support approval, such as confirmatory studies and other data or studies to address questions or concerns that may arise during the FDA review process.
−Removed: Regulatory approval may also be delayed, limited or prevented by other factors.
−Removed: For example, in 2013, 2018 and 2019, the U.S.
−Removed: federal government entered shutdowns suspending services deemed non-essential as a result of the failure by Congress to enact regular appropriations.
−Removed: Our development and commercialization activities could be harmed or delayed by a similar shutdown of the U.S.
−Removed: federal government in the future, which may significantly delay the FDA’s ability to timely review and process any submissions we have filed or may file or cause other regulatory delays, which could have a negative impact on our business.
−Removed: Even if granted, regulatory approvals may include significant limitations on the uses for which products may be marketed.
−Removed: Failure to comply with applicable regulatory requirements can, among other things, result in warning letters, imposition of civil penalties or other monetary payments, delay in approving or refusal to approve a product candidate, suspension or withdrawal of regulatory approval, product recall or seizure, operating restrictions, interruption of clinical trials or manufacturing, injunctions and criminal prosecution.
−Removed: In addition, the marketing and manufacturing of products are subject to continuing FDA review, and later discovery of previously unknown problems with a product, its manufacture or its marketing may result in the FDA requiring further clinical research or restrictions on the product or the manufacturer, including withdrawal of the product from the market.
−Removed: Failure to obtain regulatory approval in international jurisdictions would prevent our Products and our product candidates from being marketed abroad.
−Removed: In the event we pursue the right to market and sell our Products or our product candidates in jurisdictions other than the U.S., we or our potential third-party partners would be required to obtain separate marketing approvals and comply with numerous and varying regulatory requirements in each foreign country.
+Added: Failure to obtain regulatory approval in international jurisdictions would prevent our Products from being marketed abroad.
+Added: In the event we pursue the right to market and sell our Products in jurisdictions other than the U.S., we or our potential third-party partners would be required to obtain separate marketing approvals and comply with numerous and varying regulatory requirements in each foreign country.
The approval procedure varies among countries and can involve additional testing.
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jurisdictions, the commercial prospects of that product candidate may be significantly diminished and our business prospects could decline.
−Removed: Even if our product candidates in development receive regulatory approval, they may still face future development and regulatory difficulties.
−Removed: If we fail to comply with continuing federal, state and foreign regulations, we could lose our approvals to market drugs, and our business would be seriously harmed.
−Removed: Even if we obtain regulatory approval for our product candidates in development, they remain subject to ongoing requirements of the FDA and comparable foreign regulatory authorities, including requirements related to manufacturing, quality control, further development, labeling, packaging, storage, distribution, safety surveillance, import, export, advertising, promotion, recordkeeping, and reporting of safety and other postmarket information.
−Removed: Following initial regulatory approval for drugs we develop, including our Products and our product candidates, we remain subject to continuing regulatory review, including review of adverse drug experiences and clinical results that may be reported after drug products become commercially available.
+Added: If we fail to comply with continuing federal, state and foreign regulations with respect to our Products for which we obtain regulatory approval, we could lose our approvals to market drugs, and our business would be seriously harmed.
+Added: Our Products for which we obtain regulatory approval remain subject to ongoing requirements of the FDA and comparable foreign regulatory authorities, including requirements related to manufacturing, quality control, further development, labeling, packaging, storage, distribution, safety surveillance, import, export, advertising, promotion, recordkeeping, and reporting of safety and other postmarket information.
+Added: Following initial regulatory approval for drugs we develop, including our Products, we remain subject to continuing regulatory review, including review of adverse drug experiences and clinical results that may be reported after drug products become commercially available.
This would include results from any postmarketing tests or continued actions required as a condition of approval.
The manufacturer and manufacturing facilities we use to make any of our drug candidates will also be subject to periodic review and inspection by the FDA.
−Removed: If a previously unknown problem or problems with a Product or a manufacturing and laboratory facility used by us is discovered, the FDA or foreign regulatory agency may impose restrictions on that Product or on the manufacturing facility, including requiring us to withdraw the Product from the market.
+Added: If a previously unknown problem or problems with a Product
+Added: or a manufacturing and laboratory facility used by us is discovered, the FDA or foreign regulatory agency may impose restrictions on that Product or on the manufacturing facility, including requiring us to withdraw the Product from the market.
Any changes to an approved product, including the way it is manufactured or promoted, often require FDA approval before the product, as modified, can be marketed.
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These events, including the reporting of adverse safety events, among others, could result in Product recalls, product liability actions related to our Products or withdrawals or additional regulatory controls (including additional regulatory scrutiny and requirements for additional labeling), all of which could have a negative impact on our business, financial condition, cash flows and results of operations.
−Removed: The pharmaceutical industry is subject to significant regulation and oversight pursuant to anti-kickback laws, false claims statutes and anti-corruption laws, which may result in significant additional expense and limit our ability to commercialize our Products and our product candidates.
+Added: The pharmaceutical industry is subject to significant regulation and oversight pursuant to anti-kickback laws, false claims statutes and anti-corruption laws, which may result in significant additional expense and limit our
+Added: ability to commercialize our Products.
In addition, any failure to comply with these regulations could result in substantial fines or penalties.
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Healthcare providers, physicians and third-party payors play a primary role in the recommendation and prescription of any drug product with marketing approval.
−Removed: Our future arrangements with third-party payors and customers may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute our Products and product candidates with marketing approval.
+Added: Our future arrangements with third-party payors and customers may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute our Products with marketing approval.
Restrictions under applicable federal, state and foreign healthcare laws and regulations include, but are not limited to, the following:
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In addition, PPACA provides that a claim including items or services resulting from a violation of the federal anti-kickback statute constitutes a false or fraudulent claim for purposes of the false claims statutes.
−Removed: Finally, some states, such as California, Massachusetts and Vermont, mandate implementation of commercial compliance programs to ensure compliance with these laws.
+Added: some states, such as California, Massachusetts and Vermont, mandate implementation of commercial compliance programs to ensure compliance with these laws.
In addition, a number of states have laws that require pharmaceutical companies to track and report payments, gifts and other benefits provided to physicians and other health care professionals and entities.
The FCPA and similar anti-bribery laws in other jurisdictions generally prohibit companies and their intermediaries from providing money or anything of value to officials of foreign governments, foreign political parties, or international organizations with the intent to obtain or retain business or seek a business advantage.
−Removed: Recently, there has been a substantial increase in anti-bribery law enforcement activity by U.S.
−Removed: regulators, with more frequent and aggressive investigations and enforcement proceedings by both the Department of Justice and the SEC.
A determination that our operations or activities are not, or were not, in compliance with U.S.
1 unchanged sentence
Other internal or government investigations or legal or regulatory proceedings, including lawsuits brought by private litigants, may also follow as a consequence.
−Removed: Changes in laws affecting the healthcare industry could also adversely affect our revenues and profitability, including new laws, regulations or judicial decisions, or new interpretations of existing laws, regulations or
−Removed: decisions related to patent protection and enforcement, healthcare availability, and drug product pricing and marketing.
−Removed: Changes in FDA regulations and regulations issued by other regulatory agencies inside and outside of the U.S., including new or different approval requirements, timelines and processes, may also delay or prevent the approval of our product candidates, require additional safety monitoring, labeling changes, restrictions on product distribution or other measures that could increase our costs of doing business and adversely affect the market for our Products and our product candidates.
+Added: Changes in laws affecting the healthcare industry could also adversely affect our revenues and profitability, including new laws, regulations or judicial decisions, or new interpretations of existing laws, regulations or decisions related to patent protection and enforcement, healthcare availability, and drug product pricing and marketing.
+Added: Changes in FDA regulations and regulations issued by other regulatory agencies inside and outside of the U.S., including new or different approval requirements, timelines and processes, may also require additional safety monitoring, labeling changes, restrictions on product distribution or other measures that could increase our costs of doing business and adversely affect the market for our Products.
The enactment in the U.S.
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We may incur significant liability if it is determined that we are promoting the “off-label” use of drugs or promoting in a non-truthful and misleading way.
−Removed: We are prohibited from promoting our Products and any product candidates that receive regulatory approval for “off-label” uses or promoting in a non-truthful and misleading way that are not described in its labeling and that differ from the uses approved by the FDA.
+Added: We are prohibited from promoting our Products that receive regulatory approval for “off-label” uses or promoting in a non-truthful and misleading way that are not described in its labeling and that differ from the uses approved by the FDA.
Physicians may prescribe drug products for off-label uses, and such off-label uses are common across medical specialties.
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Such enforcement actions could cause us reputational harm and divert the attention of our management from our business operations.
−Removed: Likewise, our distribution and contracting partners and those providing vendor support services may also be the subject of regulatory investigations involving, or remedies or sanctions for, off-label promotion of our Products or product candidates, which may adversely impact sales of our Products or product candidates or trigger indemnification obligations.
+Added: Likewise, our distribution and contracting partners and those providing
+Added: vendor support services may also be the subject of regulatory investigations involving, or remedies or sanctions for, off-label promotion of our Products, which may adversely impact sales of our Products or trigger indemnification obligations.
These consequences, could, in turn, have a negative impact on our business, financial condition and results of operations and could cause the market value of our common shares to decline.
−Removed: Health care reform could increase our expenses and adversely affect the commercial success of our Products and our product candidates.
+Added: Health care reform could increase our expenses and adversely affect the commercial success of our Products.
and some foreign jurisdictions are considering or have enacted a number of reform proposals to change the healthcare system.
There is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality or expanding access.
−Removed: In the U.S., the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by federal and state legislative initiatives, including those designed to limit the pricing, coverage, and reimbursement of pharmaceutical and biopharmaceutical
−Removed: products, especially under government-funded healthcare programs, and increased governmental control of drug pricing.
+Added: In the U.S., the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by federal and state legislative initiatives, including those designed to limit the pricing, coverage, and reimbursement of pharmaceutical and biopharmaceutical products, especially under government-funded healthcare programs, and increased governmental control of drug pricing.
For example, the PPACA includes numerous provisions that affect pharmaceutical companies.
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The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program.
−Removed: These and other aspects of the PPACA, including the regulations that may be imposed in connection with the implementation of the PPACA, could increase our expenses and adversely affect our ability to successfully commercialize our Products and our product candidates.
+Added: These and other aspects of the PPACA, including the regulations that may be imposed in connection with the implementation of the PPACA, could increase our expenses and adversely affect our ability to successfully commercialize our Products.
There have been, and we anticipate that there will be, healthcare reform measures that may be adopted in the future that may result in more rigorous coverage criteria and additional downward pressure on the reimbursement for healthcare products and services.
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Moreover, in the U.S., there have been several presidential executive orders, congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for products.
+Added: Drug development involves a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results.
+Added: Conducting clinical trials is a lengthy, time-consuming and expensive process.
+Added: For example, we incurred significant expenses in developing our Products, with no guarantees that doing so would result in a commercially viable product.
+Added: Before obtaining regulatory approvals for the commercial sale of any products, we, or our potential partners, must demonstrate through preclinical testing and clinical trials that our product candidates are safe and effective for their intended uses in humans.
+Added: We have incurred and will continue to incur substantial expense and devote a significant amount of time to preclinical testing and clinical trials.
+Added: The outcome of clinical testing is inherently uncertain.
+Added: Failure can occur at any time during the clinical trial process.
+Added: The results of preclinical studies and early clinical trials of product candidates may not be predictive of the results of later-stage clinical trials.
+Added: In addition, regulations are not static, and regulatory agencies, including the FDA, alter their staff, interpretations and practices and may in the future impose more stringent requirements than are currently in effect, which may adversely affect our planned drug development and/or our commercialization efforts.
+Added: Satisfying regulatory requirements typically takes a significant number of years and can vary substantially based on the type, complexity and novelty of the product candidate.
+Added: Our business, results of operations and financial
+Added: condition could be materially and adversely affected by any delays in, or termination of, our clinical trials.
+Added: Factors that could impede our ability to generate commercially viable products through the conduct of clinical trials include:
+Added: • insufficient funds to conduct clinical trials;
+Added: • the inability to find partners, if necessary, for support, including research, development, manufacturing or clinical needs;
+Added: • the failure of tests or studies necessary to submit an NDA, such as clinical studies, bioequivalence studies in support of a 505(b)(2) regulatory filing, or stability studies;
+Added: • the failure of clinical trials to demonstrate the safety and efficacy of our product candidates to the extent necessary to obtain regulatory approvals;
+Added: • the failure by us or third-party investigators, CROs, or other third parties involved in the research to adhere to regulatory requirements applicable to the conduct of clinical trials;
+Added: • the failure of preclinical testing and early clinical trials to predict results of later clinical trials;
+Added: • any delay in completion of clinical trials caused by a regional, national or global disturbance where we or our collaborative partners are enrolling patients in clinical studies, such as a pandemic (including COVID-19), terrorist activities, cyberattack, or war, political unrest, a natural or man-made disaster or any other reason or event, resulting in increased costs;
+Added: • any delay in obtaining advice from the FDA or similar regulatory authorities;
+Added: • the inability to obtain regulatory approval of our product candidates following completion of clinical trials, or delays in obtaining such approvals.
+Added: From time to time, even if a product candidate has not failed, we may voluntarily determine to pause development, which effectively halts our ability to commercialize the product.
+Added: For example, we decided to pause the development of HTX-034 to evaluate the program and market potential going forward.
+Added: There can be no assurance that our decisions with respect to such pauses, and subsequent resumptions, if any, will yield the most favorable result for the Company.
+Added: There can be no assurance, that if our clinical trials are successfully initiated and completed, we will be able to obtain approval by the FDA in the U.S.
+Added: or similar regulatory authorities elsewhere in the world in a timely manner, if at all.
+Added: If we fail to successfully develop and commercialize one or more of our product candidates, we may be unable to generate sufficient revenues to attain profitability, and our reputation in the industry and in the investment community would likely be significantly damaged, each of which would cause our stock price to significantly decrease.
+Added: Delays in, or suspensions and terminations of, clinical testing could increase our costs and delay our ability to obtain regulatory approval for, and commercialize, our product candidates.
+Added: Before we can receive regulatory approval for the commercial sale of our product candidates, the FDA and comparable authorities in non-U.S.
+Added: jurisdictions require extensive preclinical safety testing and clinical trials to demonstrate their safety and efficacy.
+Added: Significant delays in preclinical and clinical testing could materially impact our product development costs and delay regulatory approval of our product candidates.
+Added: Our ability to complete clinical trials in a timely manner, or at all, has in the past been, and could in the future be impacted by, among other factors:
+Added: • delay or failure in reaching agreement with the FDA or comparable foreign regulatory authority on a trial design that we are able to execute;
+Added: • delay or failure in obtaining authorization to commence a trial or inability to comply with conditions imposed by a regulatory authority regarding the scope or design of a clinical study;
+Added: • delay or failure in reaching agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;
+Added: • delay or failure in obtaining IRB approval or the approval of other reviewing entities, including comparable foreign entities, to conduct a clinical trial at each site;
+Added: • withdrawal of clinical trial sites from our clinical trials as a result of changing standards of care or the ineligibility of a site to participate in our clinical trials;
+Added: • delay or failure in obtaining clinical materials;
+Added: • delay or failure in recruiting and enrolling suitable subjects to participate in a trial;
+Added: • delay or failure of subjects completing a trial or returning for post-treatment follow-up;
+Added: • clinical sites and investigators deviating from trial protocol, failing to conduct the trial in accordance with regulatory requirements, or dropping out of a trial;
+Added: • inability to identify and maintain a sufficient number of trial sites, many of which may already be engaged in other clinical trial programs, including some that may be for the same indication;
+Added: • failure of our third-party clinical trial managers to satisfy their contractual duties or meet expected deadlines;
+Added: • delay or failure in adding new clinical trial sites;
+Added: • ambiguous or negative interim results or results that are inconsistent with earlier results;
+Added: • feedback from the FDA, the IRB, data safety monitoring boards or comparable foreign entities, or results from earlier stage or concurrent preclinical and clinical studies that might require modification to the protocol;
+Added: • decisions by the FDA, the IRB, comparable foreign regulatory entities, or recommendations by a data safety monitoring board or comparable foreign regulatory entity to suspend or terminate clinical trials at any time for safety issues or for any other reason;
+Added: • unacceptable risk-benefit profiles or unforeseen safety issues or adverse side effects;
+Added: • failure to demonstrate a benefit from using a drug;
+Added: • manufacturing issues, including problems with manufacturing or obtaining from third parties sufficient quantities of a product candidate for use in clinical trials;
+Added: • changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
+Added: We rely on CROs and clinical trial sites to ensure the proper and timely conduct of our clinical trials and while we have agreements governing their activities, we have limited influence over CROs’ actual performance.
+Added: Our failure to successfully establish, recruit for, and oversee our clinical trials could delay our product development efforts and negatively impact our business.
+Added: If we experience delays in the completion of any ongoing study, the commercial prospects of our product candidates or any of our other future product candidates could be harmed, and our ability to generate product revenue will be delayed.
+Added: Any delays in completing our clinical trials will increase our costs, slow our product candidates’ development and approval process and jeopardize our ability to commence product sales and generate revenues.
+Added: Any of these occurrences may harm our business, financial condition and prospects significantly.
+Added: We may not obtain regulatory approval for our product candidates in development.
+Added: Regulatory approval may also be delayed or revoked or may impose limitations on the indicated uses of a product candidate.
+Added: If we are unable to obtain regulatory approval for our product candidates in development, our business will be substantially harmed.
+Added: The process for obtaining regulatory approval of a new drug is time-consuming, is subject to unanticipated delays and costs and requires the commitment of substantial resources.
+Added: Any product that we or our potential future collaborative partners develop must receive all necessary regulatory agency approvals or clearances before it may be marketed in the U.S.
+Added: or other countries.
+Added: Human pharmaceutical products are subject to rigorous preclinical and clinical testing and other requirements by the FDA in the U.S.
+Added: and similar health authorities in foreign countries.
+Added: We may not receive necessary regulatory approvals or clearances to market our product candidates currently in development in the U.S.
+Added: or in other jurisdictions, as a result of changes in regulatory policies prior to approval or other events.
+Added: Additionally, data obtained from preclinical and clinical activities, or from stability or bioequivalence studies, are susceptible to varying interpretations that could delay, limit or prevent regulatory agency approvals or clearances.
+Added: Our product candidates could fail to receive regulatory approval from the FDA or a comparable foreign regulatory authority for many reasons, including:
+Added: • disagreement with the design or implementation of our clinical trials;
+Added: • failure to demonstrate that the product candidate is safe and effective for its proposed indication;
+Added: • failure of clinical trial results to meet the level of statistical significance required for approval;
+Added: • the failure of third parties to manage and conduct the trials or perform necessary oversight to meet expected deadlines or to comply with regulatory requirements;
+Added: • failure to demonstrate that the product candidate’s clinical and other benefits outweigh its safety risks;
+Added: • disagreement with our interpretation of data from preclinical studies or clinical trials;
+Added: • the insufficiency of data collected from clinical trials to support the submission and filing of an NDA or other submission or to obtain regulatory approval;
+Added: • disapproval of the manufacturing processes or facilities of third-party manufacturers with whom we contract for clinical and commercial supplies;
+Added: • changes in approval policies or regulations that render our preclinical and clinical data insufficient for approval.
+Added: The FDA or a comparable non-U.S.
+Added: regulatory authority may require additional preclinical or clinical data to support approval, such as confirmatory studies and other data or studies to address questions or concerns that may arise during the FDA review process.
+Added: Regulatory approval may also be delayed, limited or prevented by other
+Added: For example, in 2013, 2018 and 2019, the U.S.
+Added: federal government entered shutdowns suspending services deemed non-essential as a result of the failure by Congress to enact regular appropriations.
+Added: Our development and commercialization activities could be harmed or delayed by a similar shutdown of the U.S.
+Added: federal government in the future, which may significantly delay the FDA’s ability to timely review and process any submissions we have filed or may file or cause other regulatory delays, which could have a negative impact on our business.
+Added: Even if granted, regulatory approvals may include significant limitations on the uses for which products may be marketed.
+Added: Failure to comply with applicable regulatory requirements can, among other things, result in warning letters, imposition of civil penalties or other monetary payments, delay in approving or refusal to approve a product candidate, suspension or withdrawal of regulatory approval, product recall or seizure, operating restrictions, interruption of clinical trials or manufacturing, injunctions and criminal prosecution.
+Added: In addition, the marketing and manufacturing of products are subject to continuing FDA review, and later discovery of previously unknown problems with a product, its manufacture or its marketing may result in the FDA requiring further clinical research or restrictions on the product or the manufacturer, including withdrawal of the product from the market.
+Added: Our use of hazardous materials could subject us to liabilities, fines and sanctions.
+Added: Our laboratory and clinical testing sometimes involve use of hazardous, radioactive or otherwise toxic materials.
+Added: We are subject to federal, state and local laws and regulations governing how we use, manufacture, handle, store and dispose of these materials.
+Added: Although we believe that our safety procedures for handling and disposing of such materials comply in all material respects with all federal, state and local regulations and standards, there is always the risk of accidental contamination or injury from these materials.
+Added: In the event of an accident, we could be held liable for any damages that result, and we could also be subject to fines and penalties and such liability and costs could exceed our financial resources.
+Added: If we fail to comply with these regulations and standards or with the conditions attached to our operating licenses, the licenses could be revoked, and we could be subjected to criminal sanctions and substantial financial liability or be required to suspend or modify our operations.
+Added: Compliance with environmental and other laws may be expensive and current or future regulations may impair our product development efforts.
Our employees may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have a negative impact on our business.
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We are and may become subject to stringent and evolving laws, regulations, rules, contractual obligations, policies and other obligations related to data privacy and security.
−Removed: Our actual or perceived failure to comply with such obligations could lead to regulatory investigations or actions, litigation, fines and penalties, disruptions of our business operations, reputational harm, loss of revenue or profits, and other adverse business consequences.
−Removed: In the ordinary course of business, we collect, receive, store, process, generate, use, transfer, disclose, make accessible, protect, secure, dispose of, transmit, and share (collectively, processing) personal data and other sensitive information, including proprietary and confidential business data, trade secrets, intellectual property, sensitive
−Removed: third-party data, business plans, transactions and financial information (collectively, sensitive data).
+Added: Our actual or perceived failure to comply with
+Added: such obligations could lead to regulatory investigations or actions, litigation, fines and penalties, disruptions of our business operations, reputational harm, loss of revenue or profits, and other adverse business consequences.
+Added: In the ordinary course of business, we collect, receive, store, process, generate, use, transfer, disclose, make accessible, protect, secure, dispose of, transmit, and share (collectively, "processing") personal data and other sensitive information, including proprietary and confidential business data, trade secrets, intellectual property, sensitive third-party data, business plans, transactions and financial information (collectively, "sensitive data").
Our data processing activities may subject us to numerous data privacy and security obligations, such as various laws, regulations, guidance, industry standards, external and internal privacy and security policies, contractual requirements, and other obligations relating to data privacy and security.
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The CCPA provides for civil penalties of up to $7,500 per violation and allows private litigants affected by certain data breaches to recover significant statutory damages.
−Removed: In addition, the CPRA, which became operative January 1, 2023, will expand the CCPA’s requirements, including applying to personal information of business representatives and employees and establishing a new regulatory agency to implement and enforce the law.
+Added: In addition, the CPRA, which became operative January 1, 2023, expanded the CCPA’s requirements, including applying to personal information of business representatives and employees and establishing a new regulatory agency to implement and enforce the law.
Other states, such as Virginia and Colorado, have also passed comprehensive data privacy and security laws, and similar laws are being considered in several other states, as well as at the federal and local levels.
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in compliance with law, such as the EEA and UK’s standard contractual clauses, these mechanisms are subject to legal challenges, and there is no assurance that we can satisfy or rely on these measures to lawfully transfer personal data to the U.S.
−Removed: If there is no lawful manner for us to transfer personal data from the EEA, the UK, or other jurisdictions to the U.S., or if the requirements for a legally-compliant transfer are too onerous, we could face significant adverse consequences, including the interruption or degradation of our operations, the need to relocate part of or all of our business or data processing activities to other jurisdictions at significant expense, increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, and injunctions against our processing or transferring of personal data necessary to operate our business.
+Added: If there is no lawful manner for us to transfer personal data from the EEA, the UK, or other jurisdictions to the U.S., or if the requirements for a legally-compliant transfer are too onerous, we could face significant adverse consequences, including the interruption or degradation of our operations, the need to relocate part of or all of our business or data processing activities to other jurisdictions at significant expense,
+Added: increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, and injunctions against our processing or transferring of personal data necessary to operate our business.
Some European regulators have prevented companies from transferring personal data out of Europe for allegedly violating the GDPR’s cross-border data transfer limitations.
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In particular, severe ransomware attacks are becoming increasingly prevalent and can lead to significant interruptions in our operations, loss of sensitive data and income, reputational harm, and diversion of funds.
−Removed: Extortion payments may alleviate the negative impact of a ransomware attack, but we may be unwilling or unable to make such payments due to, for example, applicable laws or regulations prohibiting such payments.
−Removed: Remote work has become more common and has increased risks to our information technology systems and data, as more of our employees utilize network connections, computers, and devices outside our premises or network, including working at home, while in transit and in public locations.
−Removed: Additionally, future or past business
−Removed: transactions (such as acquisitions or integrations) could expose us to additional cybersecurity risks and vulnerabilities, as our systems could be negatively affected by vulnerabilities present in acquired or integrated entities’ systems and technologies.
+Added: Extortion payments may alleviate the negative impact of a ransomware
+Added: attack, but we may be unwilling or unable to make such payments due to, for example, applicable laws or regulations prohibiting such payments.
+Added: The increase in remote work has increased risks to our information technology systems and data, as more of our employees utilize network connections, computers, and devices outside our premises or network, including working at home, while in transit and in public locations.
+Added: Additionally, future or past business transactions (such as acquisitions or integrations) could expose us to additional cybersecurity risks and vulnerabilities, as our systems could be negatively affected by vulnerabilities present in acquired or integrated entities’ systems and technologies.
Further, our reliance on third-party service providers could introduce new cybersecurity risks and vulnerabilities, including supply-chain attacks, and other threats to our business operations.
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In addition to experiencing a security incident, third parties may gather, collect, or infer sensitive information about us from public sources, data brokers, or other means that reveals competitively sensitive details about our organization and could be used to undermine our competitive advantage or market position.
−Removed: Our use of hazardous materials could subject us to liabilities, fines and sanctions.
−Removed: Our laboratory and clinical testing sometimes involve use of hazardous, radioactive or otherwise toxic materials.
−Removed: We are subject to federal, state and local laws and regulations governing how we use, manufacture, handle, store and dispose of these materials.
−Removed: Although we believe that our safety procedures for handling and disposing of such materials comply in all material respects with all federal, state and local regulations and standards, there is always the risk of accidental contamination or injury from these materials.
−Removed: In the event of an accident, we could be held liable for any damages that result, and we could also be subject to fines and penalties and such liability and costs could exceed our financial resources.
−Removed: If we fail to comply with these regulations and standards or with the conditions attached to our operating licenses, the licenses could be revoked, and we could be subjected to criminal sanctions and substantial financial liability or be required to suspend or modify our operations.
−Removed: Compliance with environmental and other laws may be expensive and current or future regulations may impair our product development efforts.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: For example, U.S.
+Added: 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.
+Added: 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.
+Added: There are currently a number of laws and regulations in the U.S.
+Added: that have recently been adopted with the change in presidential administration but not yet implemented or 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.
+Added: 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.
+Added: 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.
+Added: Such changes may also impact our business by creating increased volatility and uncertainty in the markets in which we operate.
+Added: 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.
+Added: administration, or estimate the overall impact of any such changes on our business, results of operations and financial condition
Risks Related to Our Intellectual Property
If we are unable to adequately protect or enforce our intellectual property rights, we may lose valuable assets or incur costly litigation to protect our rights.
−Removed: Our success will depend in part on our ability to obtain patents and maintain trade secret protection, as well as successfully defending these patents against challenges, while operating without infringing the proprietary rights of others.
−Removed: We have filed a number of U.S.
−Removed: patent applications on inventions relating to the composition of a variety of polymers, specific products, product groups and processing technology.
−Removed: As of December 31, 2023, we had a total of 34 issued U.S.
−Removed: patents and an additional 118 issued (or registered) foreign patents.
−Removed: The patents on the bioerodible technologies expire in March 2026.
−Removed: Currently, CINVANTI is covered by 10 patents issued in the U.S.
−Removed: and by five patents issued (or registered) in foreign countries including Korea and Japan.
−Removed: patents covering CINVANTI have expiration dates ranging from September 2035 to February 2036;
−Removed: foreign patents covering CINVANTI have expiration dates ranging from September 2035 to February 2036.
−Removed: Currently, SUSTOL is covered by 6 patents issued in the U.S.
−Removed: and by 18 patents issued (or registered) in foreign countries including France, Germany, Hong Kong, Ireland, Italy, Japan, Spain, Sweden, Switzerland, Taiwan, and the United Kingdom.
−Removed: patents covering SUSTOL expire in September 2024;
−Removed: foreign patents covering SUSTOL expire in September 2025.
−Removed: Currently, ZYNRELEF is protected by 16 patents issued in the U.S.
−Removed: and by 94 patents issued (or registered) in foreign countries including Albania, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungary, Iceland, Ireland, Italy, Japan, Korea, Latvia, Lithuania, Luxembourg, Macedonia, Malta, Mexico, Monaco, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Taiwan, Turkey and the United Kingdom.
−Removed: patents covering ZYNRELEF have expiration dates ranging from March 2034 to April 2035;
−Removed: foreign patents covering ZYNRELEF have expiration dates ranging from November 2033 to November 2036.
−Removed: APONVIE is covered by 10 patents issued in the U.S.
−Removed: and by five patents issued (or registered) in foreign countries including Korea and Japan.
−Removed: patents covering APONVIE have expiration dates ranging from September 2035 to February 2036;
−Removed: foreign patents covering APONVIE have expiration dates ranging from September 2035 to February 2036.
−Removed: HTX-034 is protected by 12 patents issued in the U.S.
−Removed: and by 89 patents issued (or registered) in foreign countries including Albania, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungary, Iceland, Ireland, Italy, Japan, Korea, Latvia, Lithuania, Luxembourg, Macedonia, Malta, Mexico, Monaco, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Taiwan, Turkey and the United Kingdom.
−Removed: patents covering HTX-034 have expiration dates ranging from March 2034 to April 2035;
−Removed: foreign patents covering HTX-034 have expiration dates ranging from November 2033 to November 2036.
Our policy is to actively seek patent protection in the U.S.
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Consequently, we cannot be certain that the patent applications we are pursuing will lead to the issuance of any patent or be free from infringement or other claims from other parties.
−Removed: Our competitors may also independently develop products similar to ours or design around or otherwise circumvent patents issued to us or licensed by us.
+Added: Our competitors may also independently develop products similar to
+Added: ours or design around or otherwise circumvent patents issued to us or licensed by us.
In addition, the laws of some foreign countries may not protect our proprietary rights to the same extent as U.S.
+Added: We may have to enforce our intellectual property rights against third parties who infringe our patents and other intellectual property or challenge our patent or trademark applications.
+Added: For example, in the U.S., putative generics of innovator drug products (including products in which the innovation comprises a new drug delivery method for an existing product, such as the drug delivery market occupied by us) may file Abbreviated New Drug Applications (“ANDA”) and, in doing so, certify that their products either do not infringe the innovator’s patents or that the innovator’s patents are invalid.
+Added: This often results in litigation between the innovator and the ANDA applicant.
+Added: This type of litigation is commonly known as “Paragraph IV” litigation in the U.S.
+Added: On July 27, 2022, we filed a complaint for patent infringement of certain CINVANTI patents against Fresenius Kabi USA, LLC (“Fresenius Kabi”) and a related entity in the District of Delaware in response to Fresenius Kabi’s ANDA filing seeking approval to manufacture, use or sell a generic version of CINVANTI in the U.S.
+Added: prior to expiration of the CINVANTI patents.
+Added: While in December 2024, the District Court found that the Company’s CINVANTI patents are valid and would be infringed by Fresenius Kabi’s proposed generic product, this decision is currently pending appeal and there is no guarantee that other similar or future litigation will be resolved in our favor.
+Added: These litigations, of which there are often multiple in process at one time, could result in new or additional generic competition to any of our Products and our product candidates and a potential reduction in product revenue.
+Added: For example, there is pending litigation relating to the Company’s CINVANTI patents against Mylan Pharmaceuticals Inc., and Azurity Pharmaceuticals, Inc.
+Added: (and its subsidiaries).
We may enter into collaborative agreements that may subject us to obligations that must be fulfilled and require us to manage complex relationships with third parties.
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may be less willing to protect trade secrets.
−Removed: Costly and time-consuming litigation could be necessary to seek to enforce and determine the scope of our proprietary rights.
+Added: Costly and time-consuming litigation could be necessary to seek to enforce and determine the scope of our
+Added: proprietary rights.
Any failure to enforce or protect our rights could cause us to lose the ability to exclude others from using our technology to develop or sell competing products.
−Removed: We may infringe on the intellectual property rights of others, and any litigation could force us to stop developing or selling potential products and could be costly, divert management attention and harm our business.
+Added: We may be subject to claims that we have infringed on the intellectual property rights of others, and any litigation could force us to stop developing or selling potential products and could be costly, divert management attention and harm our business.
We must be able to develop products without infringing the proprietary rights of other parties.
Because the markets in which we operate involve established competitors with significant patent portfolios, including patents relating to the composition of a variety of polymers, specific products, product groups and processing technology, it could be difficult for us to use our technologies or develop products without infringing the proprietary rights of others.
−Removed: Therefore, there is risk that third parties may make claims of infringement against our Products, our product
−Removed: candidates or our technologies.
+Added: Therefore, there is risk that third parties may make claims of infringement against our Products, our product candidates or our technologies.
We may not be able to design around the patented technologies or inventions of others, and we may not be able to obtain licenses to use patented technologies on acceptable terms, or at all.
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In part as a result of this uncertainty, there has been, and we expect that there may continue to be, significant litigation in the pharmaceutical industry regarding patents and other intellectual property rights.
−Removed: We may have to enforce our intellectual property rights against third parties who infringe our patents and other intellectual property or challenge our patent or trademark applications.
−Removed: For example, in the U.S., putative generics of innovator drug products (including products in which the innovation comprises a new drug delivery method for an existing product, such as the drug delivery market occupied by us) may file Abbreviated New Drug Applications (“ANDA”) and, in doing so, certify that their products either do not infringe the innovator’s patents or that the innovator’s patents are invalid.
−Removed: This often results in litigation between the innovator and the ANDA applicant.
−Removed: This type of litigation is commonly known as “Paragraph IV” litigation in the U.S.
−Removed: On July 27, 2022, we filed a complaint for patent infringement of certain CINVANTI patents against Fresenius Kabi USA, LLC (“Fresenius Kabi”) and a related entity in the District of Delaware in response to Fresenius Kabi’s ANDA filing seeking approval to manufacture, use or sell a generic version of CINVANTI in the U.S.
−Removed: prior to expiration of the CINVANTI patents.
−Removed: These litigations, of which there are often multiple in process at one time, could result in new or additional generic competition to any of our Products and our product candidates and a potential reduction in product revenue.
If we are required to defend ourselves in a patent-infringement lawsuit, we could incur substantial costs, and the lawsuit could divert management attention, regardless of the lawsuit’s merit or outcome.
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Provisions of Delaware law, our certificate of incorporation and our bylaws may discourage, delay or prevent a merger or acquisition that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares.
−Removed: In addition, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace or remove our Board of Directors.
+Added: In addition, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace or remove our Board of Directors (the "Board").
These provisions include authorizing the issuance of “blank check” preferred stock without any need for action by stockholders.
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Actions of activist stockholders could impact the pursuit of our business strategies, cause us to incur substantial costs, divert our management’s attention and resources, and adversely affect our business, results of operations, liquidity, financial condition, and the trading price of our common stock.
−Removed: While we value constructive input from investors and regularly engage in dialogue with our stockholders, and we welcome their views and opinions regarding strategy and performance, we may be subject to actions or proposals from activist stockholders that may not align with our business strategies or the interests of our other stockholders, and our Board of Directors and our management are committed to acting in the best interests of all of our stockholders.
−Removed: Accordingly, there is no assurance that the actions taken by our Board of Directors and our management in seeking to maintain constructive engagement with certain stockholders will be successful in preventing the occurrence of stockholder activist campaigns.
−Removed: As previously reported, in February 2023, we entered into a Cooperation Agreement, dated February 21, 2023, with two of our stockholders, Rubric Capital Management LP and certain of its affiliates and Velan Capital Investment Management LP and certain of its affiliates (collectively, the “Investor Group”), regarding certain changes to the
−Removed: composition of our Board of Directors, including the appointment of three new independent directors, Adam Morgan, Craig Collard, and Kevin Kotler, to our Board of Directors, among other items.
+Added: While we value constructive input from investors and regularly engage in dialogue with our stockholders, and we welcome their views and opinions regarding strategy and performance, we may be subject to actions or proposals from activist stockholders that may not align with our business strategies or the interests of our other stockholders, and the Board and our management are committed to acting in the best interests of all of our stockholders.
+Added: Accordingly, there is no assurance that the actions taken by the Board and our management in seeking to maintain constructive engagement with certain stockholders will be successful in preventing the occurrence of stockholder activist campaigns.
+Added: As previously reported, in February 2023, we entered into a Cooperation Agreement, dated February 21, 2023, with two of our stockholders, Rubric Capital Management LP and certain of its affiliates and Velan Capital Investment
+Added: Management LP and certain of its affiliates (collectively, the “Investor Group”), regarding certain changes to the composition of the Board, among other items.
Proxy contests have been waged against many companies in the biopharmaceutical industry over the last few years.
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• perceived uncertainties as to the future direction of the Company and our business may result in the loss of potential acquisitions, collaborations or in-licensing opportunities, and may make it more difficult to attract and retain qualified personnel and business partners;
−Removed: • if individuals are elected or appointed to our Board of Directors with a specific agenda, it may adversely affect our ability to effectively implement our strategic plan in a timely manner and create additional value for our stockholders;
−Removed: • if individuals are elected or appointed to our Board of Directors who do not agree with our strategic plan, the ability of our Board of Directors to function effectively could be adversely affected.
+Added: • if individuals are elected or appointed to the Board with a specific agenda, it may adversely affect our ability to effectively implement our strategic plan in a timely manner and create additional value for our stockholders;
+Added: • if individuals are elected or appointed to the Board who do not agree with our strategic plan, the ability of the Board to function effectively could be adversely affected.
We cannot predict, and no assurances can be given, as to the outcome or timing of any matters relating to the foregoing actions by activist stockholders and our responses thereto or the ultimate impact on our business, results of operations, liquidity, financial condition, and trading price of our common stock.
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CYBERSECU RITY
+Added: Risk Management and Strategy
In the ordinary course of our business, we collect, use, store, and transmit digitally large amounts of confidential, sensitive, proprietary, and personal information.
2 unchanged sentences
These processes are managed and monitored by a dedicated information technology team, which is led by our Chief Financial Officer and include mechanisms, controls, technologies, systems, and other processes designed to prevent or mitigate data loss, theft, misuse, or other security incidents or vulnerabilities affecting the data and maintain a stable information technology environment.
−Removed: For example, we conduct penetration and vulnerability testing, data recovery testing, security audits, and ongoing risk assessments, including due diligence on and audits of our key technology vendors, and other contractors and suppliers.
+Added: For example, we conduct vulnerability testing, data recovery testing, security audits, and ongoing risk assessments, including due diligence on and audits of our key technology vendors, and other contractors and suppliers.
We also conduct periodic employee training on cyber and information security, among other topics.
In addition, we consult with outside advisors and experts, when appropriate to assist with assessing, identifying, and managing cybersecurity risks, including to anticipate future threats and trends, and their impact on the Company’s risk environment.
−Removed: Our Chief Financial Officer, who reports directly to the Chief Executive Officer and has over 15 years of experience managing information technology and cybersecurity matters, is responsible for assessing and managing cybersecurity risks.
−Removed: We consider cybersecurity, along with other significant risks that we face, within our overall enterprise risk management framework.
In the last fiscal year, we have not identified risks from known cybersecurity threats, including any prior cybersecurity incidents, that have materially affected us .
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Additional information on cybersecurity risks we face is discussed in Part I, Item 1A, “Risk Factors.”
−Removed: The Board of Directors, as a whole and at the committee level, has oversight for the most significant risks facing us and for our processes to identify, prioritize, assess, manage, and mitigate those risks.
−Removed: The Audit Committee, which is comprised solely of independent directors, has been designated by our Board to oversee cybersecurity risks.
+Added: Our Chief Financial Officer, who reports directly to the Chief Executive Officer and has over 15 years of experience managing information technology and cybersecurity matters, is responsible for assessing and managing cybersecurity risks.
+Added: We consider cybersecurity, along with other significant risks that we face, within our overall enterprise risk management framework.
+Added: The Board, as a whole and at the committee level, has oversight for the most significant risks facing us and for our processes to identify, prioritize, assess, manage, and mitigate those risks.
+Added: The Audit Committee, which is comprised solely of independent directors, has been designated by the Board to oversee cybersecurity risks.
The Audit Committee receives regular updates on cybersecurity and information technology matters and related risk exposures from our Chief Financial Officer.
1 unchanged sentence
PR OPERTIES .
−Removed: As of December 31, 2023, we had an operating lease for 52,148 square feet of laboratory and office space in San Diego, California, with a lease term that expires on December 31, 2025.
+Added: We have an operating lease for 52,148 square feet of laboratory and office space in San Diego, California, with a lease term that expires on December 31, 2025.
In October 2021, we entered into a sublease agreement to sublet 23,873 square feet of laboratory and office space.
1 unchanged sentence
The sublease agreement expires on December 31, 2025 and is coterminous with the operating lease for the subleased space.
−Removed: We also had an operating lease for 5,840 square feet of office space in Cary, North Carolina, with a lease term that expires on April 30, 2025.
+Added: We have an operating lease for 5,840 square feet of office space in Cary, North Carolina, with a lease term that expires on April 30, 2025.
+Added: We also have a short-term operating lease for 9,882 square feet of office space in Cary, North Carolina, with a lease term that expires on August 31, 2025.
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.