What changed in this filing

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Item 1. Business

2024-03-13 compared with 2023-03-13 · 215 added, 319 removed, 735 unchanged (42% of the section changed)

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pylori ) infection and related duodenal ulcer disease;

• RediTrex ® ( methotrexate ) injection, for the treatment of active rheumatoid, juvenile idiopathic and severe psoriatic arthritis, as well as disabling psoriasis;

• Sancuso ® ( granisetron) transdermal, for the prevention of nausea and vomiting in patients receiving certain types of chemotherapy treatment;

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• Vibativ ® ( telavancin ) injection, for the treatment of certain serious bacterial infections including hospital-acquired and ventilator-associated bacterial pneumonia, as well as complicated skin and skin structure infections.

In addition to these commercial brands, we have Phase II clinical programs underway evaluating our ifetroban product candidate for patients with cardiomyopathy associated with 1) Duchenne Muscular Dystrophy (“DMD”), a fatal, genetic neuromuscular disease, 2) Systemic Sclerosis (“SSc”) or scleroderma, a debilitating autoimmune disorder characterized by fibrosis of the skin and internal organs and 3) Aspirin-Exacerbated Respiratory Disease (“AERD”), a severe form of asthma.

In addition to these commercial brands, we have Phase II clinical programs underway evaluating our ifetroban product candidate in 1) Systemic Sclerosis (“SSc”) or scleroderma, a debilitating autoimmune disorder characterized by diffuse fibrosis of the skin and internal organs, 2) patients with cardiomyopathy associated with Duchenne Muscular Dystrophy (“DMD”), a rare, fatal, genetic neuromuscular disease results in deterioration of the skeletal, heart and lung muscles and 3) patients with Idiopathic Pulmonary Fibrosis (“IPF”), the most common form of progressive fibrosing interstitial lung disease.

Investigational new study applications have been cleared by the FDA enabling us to launch clinical studies in each of these areas.

Cumberland has built core competencies for the acquisition, development and commercialization of pharmaceutical products in the U.S.

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Our marketing and sales organization is responsible for our commercial activities, and we work closely with our distribution partners to ensure the availability and delivery of our products.

COVID-19 Pandemic

In early 2020, the U.S.

declared a health care emergency following the outbreak of SARS-CoV-2, a novel strain of coronavirus that causes COVID-19.

The Company managed through the resulting pandemic, continuing to operate our business – keeping facilities open and our organization intact.

We moved quickly to ensure the health and safety of our team.

We also maintained our ongoing compliance with the many laws and regulations that apply to us as a publicly traded pharmaceutical company.

Throughout the pandemic, Cumberland faced the same challenges affecting other companies that rely on hospital admissions and patient visits to drive revenue.

Our clinical studies were also impacted, as fewer patients sought elective surgeries and our access to medical facilities was substantially limited.

We carefully monitored our supply chain, including the flow of raw materials and the batches of finished products emerging from the facilities that manufacture our products.

We welcomed a return to a more typical operating environment as 2022 progressed, following the economic and societal effects of the pandemic.

We were encouraged to see enrollment in our clinical trials resume, patient procedures return to more customary levels and access for our sales representatives improve as they gained more face-to-face meetings with medical professionals.

In 2022, we continued to expand our product portfolio, starting the year with the announcement of our Sancuso acquisition from the U.S.

affiliate of Japan-based Kyowa Kirin.

With significant contributions from Sancuso, we experienced strong year-over-year revenue growth.

Throughout the year we continued our mission, delivering our products to improve patient care, while also addressing the interests of our shareholders, employees, partners and community.

New Headquarters

In late October 2022, we opened our new headquarter offices at the Broadwest campus in the Vanderbilt/West End corridor of Nashville.

Our move into the new state-of-the-art facilities will enable the Company to accommodate our growth, support our team, and better serve our international base of customers and partners.

Sustainability Report

In August 2022, we released our second annual Sustainability Report (the “2021 Sustainability Report”), which detailed Cumberland’s activities pertaining to our environmental, social and governance matters.

We issued our inaugural Sustainability Report in 2019 and remain committed to sustainability and to maintaining transparency of our corporate operations.

As the largest biopharmaceutical company founded and headquartered in the Mid-South, we hold ourselves to the highest standards of ethical practices and understand the importance of recognizing and addressing our impact on our constituents, the community and the environment.

The 2021 Sustainability Report noted that during that year we provided nearly 2.5 million patient doses of our products, safely disposed of over 6,000 pounds of expired and damaged products and had no product recalls.

We also had no Company brands listed on the FDA’s MedWatch Safety Alerts for Human Medical Products, no Company product issues identified by the FDA’s Adverse Event Reporting System and no clinical trials terminated due to failure to practice good clinical standards.

The 2021 Sustainability Report also highlighted our investment in our employees through our continuing education programs, employee development initiatives and employee recognition awards.

During the year we took a fresh look at our mission statement and refined it to better capture the spirit of what we do each day at Cumberland.

Our mission is now:

working together to provide unique products that improve the quality of patient care.

In designing this statement, we considered several factors.

First, we wanted our mission to address the constituencies we serve, which include patients in need of care, as well as health care providers, our employees, shareholders, partners and community.

We also sought to reflect Cumberland’s culture, where teamwork is prized, emphasized and expected – in order to achieve our goals.

Next, it needed to demonstrate our focus on developing, acquiring and distributing differentiated brands.

And finally, we wanted to emphasize that the patient is at the core of everything we do.

Our collective efforts are directed at providing unique products that serve as better alternatives for poorly met medical needs.

Sustainability Metrics

We issued our inaugural Sustainability Report in 2019, detailing Cumberland’s activities pertaining to our environmental, social and governance matters, and we remain committed to sustainability and to maintaining transparency of our corporate operations.

As one of the largest biopharmaceutical companies founded and headquartered in the Mid-South, we hold ourselves to the highest standards of ethical practices and understand the importance of recognizing and addressing our impact on our constituents, our community and the environment.

Our 2023 sustainability metrics reveal that during that year we provided 3 million patient doses of our products, while safely disposing of nearly 6,000 pounds of expired and damaged products.

We had no product recalls and no clinical trials terminated due to failure to practice good clinical standards.

In 2023, we also highlighted our investment in our employees through our continuing education programs, employee development initiatives and employee recognition awards.

We reported that women represented 44% of Cumberland’s workforce – and 15% of our employees were minorities.

Through our sustainability initiatives, we will continue to identify and address critical industry issues, monitor relevant guidelines and utilize best practices.

Cybersecurity

The Company has taken appropriate steps to monitor an adequate level of cybersecurity.

The Company is insured against cyber attacks and has appropriate detection and mitigation controls in place.

Additional Information

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Omeclamox ® -Pak

pylori Infection and Related Duodenal Ulcer Disease Marketed

Arthritis and Psoriasis Marketed

pylori Infection and Related Duodenal Ulcer Disease Approved

Nausea and Vomiting Associated with Chemotherapy Marketed

Euvolemic and Hypervolemic Hyponatremia Marketed

Euvolemic and Hypervolemic Hyponatremia Approved

Serious Bacterial Infections Marketed

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By ruling in Cumberland’s favor, the court upheld the validity of the patent that encompasses our EDTA-free formulation.

The court also granted a permanent injunction preventing challengers from marketing a generic version of our proprietary Acetadote product formulation before the expiration of Cumberland’s patent in August 2025.

An Appeals Court affirmed the District Court ruling in the Company’s favor upholding Cumberland’s Acetadote patent and expressly rejected the validity challenge.

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We then received FDA approval for the use of Caldolor in pediatric patients 6 months of age and older.

Caldolor is the first and only injectable non-steroidal anti-inflammatory drug approved for use in children.

We subsequently initiated a study to collect data on the use of Caldolor in children ranging in age from birth up to 6 months of age.

Enrollment in that study was completed in 2019.

In early 2018, we completed and filed the application for FDA approval of a next generation Caldolor product featuring an improved presentation and formulation which was approved in January 2019.

The new, premixed presentation provides healthcare professionals a formulation that is easy to administer, helping manage the treatment of patient pain and fever, while reducing opioid consumption.

The new, premixed presentation provides health care professionals a formulation that is easy to administer, helping manage the treatment of patient pain and fever, while reducing opioid consumption.

It is provided in a pre-mixed bag containing 800 mg of ibuprofen in a 200 mL patented low sodium formulation for injection that is ready to use.

It is the first and only

FDA-approved pre-mixed bag of ibuprofen.

It is the first and only FDA-approved pre-mixed bag of ibuprofen.

Caldolor is still available as an 800 mg/8mL single–dose vial for dilution in addition to the ready-to-use bag.

In January 2020, we initiated a full-scale launch of this ready-to-use product.

Unfortunately, the launch was impacted by the COVID-19 pandemic and the resulting postponement of elective surgeries.

In November 2021, the FDA approved our submission to expand the labeling for Caldolor to include administration of the product prior to surgery.

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PiSA expects to provide the product in both 400- and 800-milligram vials.

In 2023, the FDA approved expanded labeling for Caldolor to include use in infants 3 to 6 months old.

The safety and efficacy of Caldolor has now been established for the treatment of pain and fever in pediatric patients aged 3 months and older.

With this newly approved labeling, Caldolor is the only non-opioid product approved to treat pain in infants that is delivered through injection.

Also in 2023, we announced the publication of positive results from a clinical study investigating the safety and pharmacokinetics of Caldolor in infants.

Published in the journal Pediatric Drugs , the results support the FDA’s approval of Caldolor in patients 3 to 6 months of age.

In addition, we reported that we expect Caldolor will be eligible for special Medicare reimbursement under the new Non-Opioids Prevent Addiction in the Nation Act (the “NOPAIN Act”), which was enacted as part of the Consolidated Appropriations Act of 2023.

The NOPAIN Act requires Medicare to provide separate and more favorable reimbursement for non-opioid products that are used to manage pain during surgeries conducted in hospital outpatient departments or ambulatory surgical centers.

In the Medicare Hospital Outpatient Prospective Payment System Proposed Rule, the Centers for Medicare and Medicaid Services (“CMS”) requested that manufacturers with potentially applicable non-opioid products submit comments and supporting clinical evidence regarding products that should be eligible for separate payment.

We submitted a comment letter along with the requisite clinical information to the CMS in September of 2023 explaining why Caldolor should be included and separately reimbursed.

We now await further information from CMS expected this year, including the potential new reimbursement level for Caldolor.

The Act is scheduled to go into effect in early 2025 and will initially apply to those products that are furnished between January 1st, 2025 and January 1st, 2028.

Kristalose is a prescription laxative administered orally for the treatment of acute and chronic constipation.

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We then added another partner, Foxland Pharmaceuticals, Inc., who is repackaging Kristalose and featuring it with additional new physician targets.

During 2022, we continued to support Kristalose through our field sales force as well as our partnerships with Poly Pharmaceuticals and Foxland Pharmaceuticals, Inc.

The Kristalose award-winning marketing campaign was refreshed for 2022 to support increased engagement with our customers.

We also expanded patient support for the brand and it was added to the GoodRx platform during the year.

We also expanded patient support for the brand – and it was added to the GoodRx platform in 2022.

During 2023, we continued to support Kristalose through our field sales force as well as our partnerships with Poly Pharmaceuticals and Foxland Pharmaceuticals, Inc.

We have found that the brand performs best in states where we have Medicaid coverage.

New York state recently added Kristalose to its Medicaid formulary, and we are implementing a special initiative to increase our presence and share of voice in the state.

We believe that this new coverage is contributing to the growth of the product.

Omeclamox ® -Pak

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We acquired the assets and exclusive rights to Omeclamox-Pak through a series of transactions and re-launched the product as a Cumberland brand supported by our field sales force.

The packager for Omeclamox-Pak encountered financial difficulties due to the impact of COVID-19.

They are under new management and are in the process of a reorganization.

Discussions with the packager are ongoing.

We entered into an exclusive license and supply agreement to register and commercialize a methotrexate product line in the United States.

RediTrex is a line of pre-filled syringes specifically designed for ease of handling and dosing accuracy for the subcutaneous administration of methotrexate in patients with arthritis and psoriasis.

RediTrex treats patients with severe, active rheumatoid arthritis, and polyarticular juvenile idiopathic arthritis who have difficulty tolerating or responding to orally delivered methotrexate.

It is also approved for symptomatic control of severe, recalcitrant, disabling psoriasis in adults who are not adequately responsive to other forms of therapy.

With more than 54 million Americans living with some form of arthritis, the disease is among the most common causes of work disability in the U.S., according to the CDC.

The oral form of methotrexate is typically the first line of treatment for rheumatoid arthritis.

As the disease progresses, the dose must be increased to stay effective, often causing intolerable gastrointestinal side effects.

Injectable methotrexate has been proven to be more effective than oral delivery, with fewer gastrointestinal reactions.

Because of the increased efficacy and tolerability, injectable methotrexate can delay the need to move to costly biologics, lowering overall patient treatment costs.

Once disease progression requires the use of biologics, continuing the treatment of injectable methotrexate along with the biologic has been shown to increase overall efficacy.

Other injectable methotrexate options available may not optimally meet the needs of arthritis patients who are offered either a vial and syringe for self-injection, or the use of an expensive autoinjector.

The vial and syringe method can be difficult for a patient to handle due to limited dexterity in their hands.

Additionally, obtaining the exact dose needed while preventing skin exposure to the caustic methotrexate can be quite challenging for many patients.

The autoinjectors provide a better alternative to the vial and syringe, but they remove injection control from the patient and can be painful to administer.

They are also the most expensive methotrexate delivery.

In December 2019, we received FDA approval for RediTrex and began planning for a launch of the product line.

In late 2020, we received initial product supplies and then provided shipments of RediTrex to select accounts.

Due to the pandemic, we delayed the national launch of the product, which was then implemented during the fourth quarter of 2021.

During 2022, we entered into two amendments to our agreement with Nordic Pharma, who had provided us with a license for the U.S.

rights associated with our RediTrex line.

Pursuant to these amendments, in exchange for financial consideration, Nordic may assume responsibility for distributing the methotrexate products in the U.S.

after June 30, 2023.

The packager for Omeclamox-Pak encountered financial difficulties in 2020 due to the impact of COVID-19, and their operations are currently suspended.

As a result, we depleted our inventory of the product and notified the FDA that the product is currently unavailable.

That facility is now under new ownership and new management.

We are awaiting resumption of their operations, while also exploring other alternatives to restart the product’s packaging.

Given the delay in identifying a packager for Omeclamox-Pak, as a precaution, the Company has taken a non-cash write down of the related intangible asset of $ 3.3 million.

The financial statements reflect this adjustment.

At the end of 2021, we entered into an agreement with Kyowa Kirin to acquire the U.S.

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– including its marketing, promotion, distribution, manufacturing and medical support activities.

Kyowa Kirin retained international rights, continuing to deliver the product to address oncology patients’ needs throughout the rest of the world.

Kyowa Kirin retains international rights, continuing to deliver the product to address oncology patients’ needs throughout the rest of the world.

In January 2022, we began shipments of the product and formed a new sales force, Cumberland Oncology, to support the brand.

During this past year, we completed the transition of Sancuso from Kyowa Kirin to Cumberland.

We have already seen Sancuso quickly become one of our most important brands and a significant contributor to our business.

During 2023, we completed the transition of Sancuso from Kyowa Kirin to Cumberland, including the NDA transfer, and expanded our oncology sales division to further support the brand.

We also successfully transferred manufacture of the product to a new facility.

Following FDA approval of that site, we have now received new supplies of Cumberland-packaged product, which we will begin shipping this year.

We acquired the assets and rights to Vaprisol, a prescription brand indicated to raise serum sodium levels in hospitalized patients with euvolemic and hypervolemic hyponatremia.

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Vaprisol raises serum sodium to appropriate levels and promotes free water secretion.

Our Vaprisol product is one of two branded prescription products indicated for the treatment of hyponatremia, and the only intravenously administered branded treatment.

It has a proven day-one response rate to normalize serum sodium levels in hyponatremic patients and move them out of the Intensive Care Unit as efficiently as possible.

Our Vaprisol product has a proven day-one response rate to normalize serum sodium levels in hyponatremic patients and move them out of the Intensive Care Unit as efficiently as possible.

Vaprisol is supported by our hospital sales division.

Demand for the product increased in 2020 during the pandemic, and we worked to support the expanded use of the product in hospitals and clinics during the health care crisis.

During 2021, we shipped all remaining inventory of the product and have notified the FDA that supplies of the product are not currently available.

We have since transferred manufacturing of the product to a new manufacturing facility.

During 2021, we shipped all remaining inventory of the product and notified the FDA that supplies of the product are not currently available.

We have since transferred the product’s manufacturing to a new facility.

Our new manufacturing partner is working with the FDA to address several Form 483 and warning letter issues in a timely manner.

Meanwhile, we are working with them to support a special, interim supply of compounded product for critically ill patients, while awaiting the needed facility approval to relaunch Vaprisol.

Meanwhile, we have been working with them to support a special, interim supply of compounded product for critically ill patients, which we introduced to the market in late 2023 and will begin selling in early 2024.

We then expect to file for the approval to manufacture branded Vaprisol once all FDA issues at the new site are resolved.

In November 2018, the Company announced an agreement to acquire the Vibativ assets and assume global responsibility for the brand including the related marketing, distribution, manufacturing and regulatory activities.

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Pneumonia caused by secondary bacterial infections is common among patients with viral respiratory infections.

The risk of such infections grows as hospitals see more patients with respiratory symptoms due to COVID-19.

Research shows that hospital-acquired pneumonia (“HAP”) and ventilator-associated pneumonia (“VAP”) have historically accounted for 22% of common hospital-acquired infections.

Methicillin-sensitive and methicillin-resistant S.

aureus (“MSSA” and “MRSA”) are important disease-causing pathogens in these cases.

MSSA and MRSA are important disease-causing pathogens in these cases.

While many recently introduced antibiotics are quickly losing the battle to fight the bacteria they were designed to kill because those bacteria have become drug-resistant, Vibativ was specifically designed to kill drug-resistant bacteria.

The molecule of an existing antibiotic to which bacteria had developed a resistance, vancomycin, was altered by adding a lipophilic (fat-loving) component and a hydrophilic (water-loving) component.

The lipophilic addition

increases Vibativ’s ability to penetrate the cell wall and inhibits the formation of new cell walls (the development of new and/or additional cell walls is the most common way that bacteria become resistant to drugs).

The lipophilic addition increases Vibativ’s ability to penetrate the cell wall and inhibits the formation of new cell walls (the development of new and/or additional cell walls is the most common way that bacteria become resistant to drugs).

The hydrophilic addition increases Vibativ’s penetration into tissue – so it is able to attack infections that are not reachable by other antibiotics.

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Further, in clinical trials, Vibativ demonstrated superior cure rates of patients with hospital-acquired bacterial pneumonia.

In 2023, we announced a new publication in Antimicrobial Agents and Chemotherapy detailing the results of the first clinical study investigating the safety and pharmacokinetics of our Vibativ product in children 2 to 17 years of age.

The results of the study suggest that a single dose of Vibativ is safe in children and they experience reduced exposure to Vibativ, compared with the same body weight-based dosing in adults.

While we remain focused on promoting Vibativ in the U.S.

market, we are building a network of other established companies to bring Vibativ to patients in their countries and territories.

In March 2022, we announced the launch of Vibativ in Puerto Rico through a partnership with Verity Pharmaceuticals, who has a particular strength and experience in that market.

Also in March 2022, we announced a new partnership with Saudi Arabia-based Tabuk Pharmaceutical to introduce Vibativ into the Middle East.

In 2022, we announced a new partnership with Saudi Arabia-based Tabuk Pharmaceutical to introduce Vibativ into the Middle East.

The arrangement provides Tabuk exclusive rights to distribute Vibativ in Saudi Arabia and Jordan, with the option to expand into other countries in the region.

Additionally, D.B.

Pharm, our partner in South Korea who also distributes Caldolor, is awaiting the approval of Vibativ in their country.

Meanwhile, our Vibativ partner for the Chinese market, SciClone Pharmaceuticals, had their approval application in China accepted for review in September 2021.

We have since been supporting SciClone and their requests associated with review of that submission.

They are working toward the approval and SciClone believes that there is significant potential for Vibativ in their country.

They are working toward the approval and believe that there is significant potential for Vibativ in their country.

Ifetroban Clinical Studies

Ifetroban is a selective thromboxane-prostanoid receptor (“TPr”) antagonist dosed in nearly 1,400 subjects and found to be safe and well tolerated in healthy volunteers and various patient populations.

We are currently sponsoring a series of Phase II clinical programs to evaluate our ifetroban product candidates in 1) Aspirin-Exacerbated Respiratory Disease , a severe form of asthma, 2) Systemic Sclerosis or scleroderma, a debilitating autoimmune disorder characterized by diffuse fibrosis of the skin and internal organs and 3) patients with cardiomyopathy associated with Duchenne Muscular Dystrophy , a genetic neuromuscular disease that results in deterioration of the skeletal, heart and lung muscles.

Enrollment in our clinical studies was interrupted due to the COVID-19 pandemic.

However, many of our clinical study sites have reopened and resumed screening of patients for potential participation into our studies during 2022.

We also closed unproductive sites and opened qualified replacements during the year.

We have been evaluating our ifetroban product candidate in a series of clinical studies.

We have three Phase II clinical programs underway evaluating our ifetroban product candidate in 1) Systemic Sclerosis or scleroderma, a debilitating autoimmune disorder characterized by diffuse fibrosis of the skin and internal organs, 2) patients with cardiomyopathy associated with Duchenne Muscular Dystrophy , a rare, fatal, genetic neuromuscular disease results in deterioration of the skeletal, heart and lung muscles and 3) patients with Idiopathic Pulmonary Fibrosis, the most common form of progressive fibrosing interstitial lung disease.

Investigational new study applications have been cleared by the FDA enabling us to launch clinical studies in each of these areas.

We also completed a pilot Phase II study involving 1) patients suffering from Hepatorenal Syndrome, a life-threatening condition involving liver and kidney failure 2) patients with Portal Hypertension associated with chronic liver disease and 3) patients with Aspirin-Exacerbated Respiratory Disease, a severe form of asthma.

There were no significant safety issues identified with the use of ifetroban in these patients.

Additional pilot studies of ifetroban are underway, including several investigator-initiated trials.

We are awaiting results from the studies underway before deciding on the best development path for the registration of ifetroban, our first new chemical entity.

Following is more information about the clinical programs in which we are evaluating ifetroban:

Aspirin-Exacerbated Respiratory Disease (“AERD”)

We have completed the manufacturing and initiated clinical development of an oral formulation of ifetroban under the brand name Boxaban ® .

We are evaluating this candidate for patients suffering from Aspirin-Exacerbated Respiratory Disease (“AERD”), also known as Samter’s Triad, a chronic medical condition that consists of three clinical features:

asthma, sinus disease with nasal polyposis and sensitivity to aspirin.

AERD is characterized by sharp increases in inflammatory mediators and platelet activity within the respiratory system.

Approximately one in 20 asthmatic adults in the U.S.

suffer from AERD and awareness of the disease is growing within the medical community.

There is no U.S.

approved pharmaceutical treatment for AERD.

Researchers at Brigham and Women’s Hospital have completed an investigator-initiated study evaluating the impact of ifetroban on the aspirin desensitization process in patients with AERD.

This single center study closed early due to poor patient accrual and exhausted funding.

The researchers found no statistical difference in the dose of aspirin needed to provide an increase in an extended version of the patient’s total nasal symptom score.

The researchers are pursuing a publication of the full study results.

It should be noted that the results from this investigator study were inconsistent with the previously published preclinical findings that demonstrated ifetroban blockade inhibited all features of aspirin reactions in a model of AERD.

It also differs in design from our corporate-sponsored AERD studies.

We completed an initial Phase II clinical study at several U.S.

medical centers led by the Scripps Research Institute entitled, A Multicenter, Double-blind, Randomized, Placebo-Controlled Trial to Determine the Safety of Oral Ifetroban in Patients with a History of AERD .

That study randomized 16 subjects 3:1 (ifetroban:

placebo), demonstrated no safety concerns and provided several signals of efficacy.

A follow-on phase II study designed to evaluate the safety and efficacy of eight weeks of oral ifetroban entitled, A Phase 2 Multicenter, Double-blind, Randomized, Placebo- Controlled Trial to Evaluate Oral Ifetroban in Subjects with Symptomatic Aspirin Exacerbated Respiratory Disease (“AERD”) , was then initiated.

The patient enrollment in that study is now closed, and we are awaiting the completion of the data analysis and availability of top line study results.

Systemic Sclerosis (“SSc”)

We have also initiated the clinical development of ifetroban oral capsules under the brand name Vasculan ® for the treatment of Systemic sclerosis , also called scleroderma.

We have initiated the clinical development of ifetroban oral capsules under the brand name Vasculan ® for the treatment of Systemic sclerosis , also called scleroderma.

It’s a debilitating autoimmune disorder characterized by diffuse fibrosis of the skin and internal organs, including the heart, as well as vascular dysfunction.

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Our Vanderbilt collaborators completed preclinical studies demonstrating TPr blockade with ifetroban prevents cardiac fibrosis and can restore cardiac function in animal models of PAH.

The FDA cleared our Investigational New Drug (IND) application to evaluate 12 months of oral ifetroban (Vasculan) in a 34-subject phase II trial entitled, A Phase II Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Ifetroban in Patients with Diffuse Cutaneous Systemic Sclerosis or Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.

Enrollment in this study is well underway and includes patients with diffuse cutaneous SSc, as well as those with pulmonary arterial hypertension associated with their SSc.

The FDA cleared our IND application to evaluate 12 months of oral ifetroban (Vasculan) in a 34-subject phase II trial entitled, A Phase II Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Ifetroban in Patients with Diffuse Cutaneous Systemic Sclerosis or Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.

This study is well underway and includes patients with diffuse cutaneous SSc, as well as those with pulmonary arterial hypertension associated with their SSc.

Duchenne Muscular Dystrophy (“DMD”)

We also initiated the clinical development of oral ifetroban under the brand name Dyscorban ® for the treatment of cardiomyopathy associated with Duchenne Muscular Dystrophy (“DMD”), a rare and fatal disease caused by a genetic defect which leads to inexorable muscle damage.

We also initiated the clinical development of oral ifetroban under the brand name Dyscorban ® for the treatment of cardiomyopathy associated with Duchenne Muscular Dystrophy, a rare and fatal disease caused by a genetic defect which leads to inexorable muscle damage.

Cardiomyopathy is the leading cause of death in DMD patients.

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As a result of the COVID-19 pandemic and its global impact on clinical research in 2020, the FDA awarded a supplemental grant in support of our Phase II DMD study.

During 2022, patient enrollment in this DMD study continued.

Progressive Fibrosing Interstitial Lung Diseases

Idiopathic Pulmonary Fibrosis (“IPF”)

In September 2021, our Board of Directors approved a new clinical program for the use of ifetroban to treat Progressive Fibrosing Interstitial Lung Diseases (“PF-ILDs”).

Nonclinical studies are complete, and the resulting manuscript was prepared and submitted for publication in 2021.

A Phase II clinical study is planned and an application to the FDA is in preparation to support this new clinical program.

In May 2023, we announced that the FDA cleared the IND application for a Phase II study in patients with Idiopathic Pulmonary Fibrosis, the most common form of progressive fibrosing interstitial lung disease.

As a result, we are in the process of initiating our FIGHTING FIBROSIS trial designed to enroll 128 patients in over 20 medical centers of excellence across the U.S.

This Phase II clinical trial will study the safety, tolerability and efficacy of oral ifetroban in patients with IPF.

Recent studies have shown ifetroban can both prevent and enhance resolution of lung fibrosis in multiple preclinical models.

Other Ifetroban Programs

We have also completed Phase II clinical programs with ifetroban in patients with Hepatorenal Syndrome (“HRS”) and patients with Portal Hypertension (“PH”).

Additional preclinical and pilot clinical studies of ifetroban are underway, including several investigator-initiated trials.

There were no significant safety issues identified with the use of ifetroban in these patients.

Additional pilot studies of ifetroban are underway, including several investigator-initiated trials.

Our plan going forward is to complete each of our Company-sponsored studies, analyze their final data, announce top-line results and decide on the best development path for the registration of ifetroban, which we continue to believe has the potential to benefit many patients with orphan diseases that represent unmet medical needs.

New Hospital Product Candidate

Cumberland was responsible for the formulation, development and FDA approval of both Acetadote and Caldolor.

Our Medical Advisory Board has helped us identify additional opportunities that address unmet or poorly met medical needs.

As a result, Cumberland has successfully designed, formulated and completed the preclinical studies for a cholesterol-reducing agent for use in the hospital setting.

We have completed a Phase I study which defined the pharmacokinetic properties and provided a favorable safety profile for this new product candidate.

The study results and a proposed clinical development plan were discussed with the FDA.

A Phase II study has been initiated and patient enrollment is complete.

We have also completed the clinical study report, filed it with the FDA and continue to consider any next steps for this program.

FDA Fee Waivers

During 2023, the FDA informed us that it had granted two barrier-to-innovation waivers that would result in refunds totaling approximately $2.8 million that we had previously paid for prescription drug program fees.

The FDA granted each waiver after concluding that Cumberland met the statutory criteria based on the innovation associated with its ifetroban clinical development programs, as the funds could be better used to advance those studies.

We received both refunds in June 2023.

GROWTH STRATEGY

Cumberland’s growth strategy involves maximizing the potential of our existing brands while continuing to build a portfolio of differentiated products.

We currently feature eight products approved by the FDA in the United States.

We currently feature seven products approved by the FDA in the United States.

We are also continuing to explore international partnerships to bring our medicines to patients in other countries.

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We actively pursue opportunities to acquire additional marketed products as well as late-stage development product candidates in our target medical specialties.

Our clinical team is developing a pipeline of new product candidates largely to address poorly met medical needs.

Our clinical team is developing a pipeline of new product candidates to address poorly met medical needs.

We are supplementing these activities with the earlier-stage drug development at Cumberland Emerging Technologies (“CET”), our majority-owned subsidiary.

CET partners with academic research institutions to identify and support the progress of promising new product candidates, which Cumberland has the opportunity to further develop and commercialize.

CET partners with academic research institutions to identify and support the progress of promising new product candidates, which Cumberland could further develop and commercialize.

Specifically, we are seeking long-term, sustainable growth by:

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We continue to evaluate our products following their FDA approval to determine if additional clinical data could expand their market and use.

For example, we have secured pediatric approval of Acetadote and Caldolor and are expanding the labeling for both brands accordingly.

We also recently further expanded the labeling for Caldolor to allow its use prior to surgery.

For example, we have secured pediatric approval of Acetadote and Caldolor and expanded the labeling for both brands accordingly.

We also added pre-surgery dosing for Caldolor, and recently included newborns to the patients who can benefit from the product.

We will continue to explore such opportunities to bring our products to new patient populations.

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In addition to our product development activities, we are also seeking to acquire products or late-stage development product candidates to continue to build a portfolio of complementary brands.

We focus on under-promoted, FDA-approved drugs as well as late-stage development products that address poorly met medical needs.

We focus on under-promoted, FDA-approved drugs as well as late-stage development products that can improve patient care.

We will continue to target product acquisition candidates that are competitively differentiated, have valuable intellectual property or other protective features, and allow us to leverage our existing infrastructure.

Our acquisition of Sancuso is an example of this strategy.

Our acquisitions of Vibativ and Sancuso are examples of the implementation of this strategy.

• Progressing our clinical pipeline and incubating future product opportunities at CET.

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We look for strategic partners that can complement our capabilities and enhance opportunities for our brands.

For example, our co-promotion partnerships have allowed us to expand the support for Kristalose across the U.S.

For example, our co-promotion partnerships have allowed us to expand the support for Kristalose and Sancuso across the U.S.

• Building an international contribution to our business.

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We are also building a network of select international partners to register our products and make them available to patients in their countries.

We will continue to develop our network of international partners while supporting our partners’ registration and commercialization efforts in their respective territories.

We will continue to develop and expand our network of international partners while supporting our partners’ registration and commercialization efforts in their respective territories.

The acquisition of Vibativ resulted in several new international partners and market opportunities.

For example, we have new partnerships Tabuk Pharmaceutical for Vibativ in Saudi Arabia and PiSA Pharmaceutical for Caldolor in Mexico.

• Managing our operations with financial discipline.

We continually work to manage our expenses in line with our revenues in order to deliver positive cash flow from operations.

We remain in a strong financial position, with favorable gross margins and positive cash flow from operations.

We continually work to manage our expenses in line with our revenues to deliver positive cash flow from operations.

We remain in a strong financial position, with favorable gross margins and a strong balance sheet.

SALES AND MARKETING

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and is comprised of both inside and field-based sales professionals.

The division is initially comprised of seven individuals who formerly supported Sancuso for Kyowa Kirin.

This initial group can be expanded through additional personnel or augmented through co-promotion arrangements.

During 2023, we expanded the sales division as we work to deliver Sancuso to cancer patients, helping them tolerate their chemotherapy treatments.

The division is comprised of 12 individuals, including four inside reps.

This group can be expanded through additional personnel or augmented through co-promotion partners.

Our commercial executives conduct ongoing analyses to evaluate marketing campaigns and promotional programs in support of our brands.

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Phebra Pty Ltd Acetadote & Caldolor Australia Marketed

DB Pharm Korea Co., Ltd.

Pharm Korea Co., Ltd.

Caldolor South Korea Marketed

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Caldolor India Marketed

GerminMED Caldolor Qatar Marketed

R-Pharm JSC Vibativ Russia Marketed

Tabuk Pharmaceuticals, Inc.

Vibativ Saudi Arabia and Jordan Registration

R-Pharm JSC Vibativ Russia and CIS Marketed

Tabuk Pharmaceuticals Vibativ Saudi Arabia and Jordan Registration

PiSA Pharmaceutical Caldolor Mexico Registration

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Vibativ China and Hong Kong Registration

DB Pharm Korea Co., Ltd.

Vibativ & Vaprisol South Korea Registration

Pharm Korea Co., Ltd.

Vaprisol & Vibativ South Korea Registration

WinHealth Pharma Group Co.

Caldolor & Acetadote China and Hong Kong Development

Acetadote China and Hong Kong Development

Our international commercialization agreements include a license to one or more Cumberland products for a specific territory as noted in the table above.

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During 2022, we worked with them to prepare the submissions for the approval of each brand there.

They are currently awaiting the approval of Vibativ in their country.

We have executed a license and distribution agreement with HongKong WinHealth Pharma Group Co.

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In February 2021, SciClone completed an initial public offering and listing of their shares on the Hong Kong stock exchange.

In June 2021, SciClone submitted an application to the Chinese regulatory authority for the approval of Vibativ in that country.

In June 2021, SciClone submitted an application to the

Chinese regulatory authority for the approval of Vibativ in that country.

In October 2021, SciClone informed us that the filing was accepted by the regulatory agency for review.

SciClone is in the review period of their application and believes that the potential for Vibativ in China may be significant.

In August 2021, we signed an agreement with Verity Pharmaceuticals International Limited (“Verity”) to license and commercialize our Vibativ product in Puerto Rico.

Verity is a specialty pharmaceutical company with commercial operations in the U.S.

They have a particular strength and experience in the Puerto Rican market.

In March 2022, we established distribution for our Vibativ product in the Middle East through a partnership with Tabuk Pharmaceutical Manufacturing Company.

We have since been supporting SciClone and their requests associated with review of that submission.

They are working toward the approval, responding to regulatory inquiries, and believe that there is significant potential for Vibativ in their country.

In March 2022, we established distribution for our Vibativ product in the Middle East through a partnership with Tabuk Pharmaceutical Manufacturing Company (“Tabuk”).

Through our partnership, Tabuk will introduce the product in Saudi Arabia, Jordan and potentially other countries in the Middle East.

They are currently updating their product approval in Saudi Arabia with new manufacturing information.

In October 2022, we announced an agreement with PiSA Pharmaceutical for the registration and commercialization of Caldolor in Mexico.

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PiSA will be responsible for obtaining regulatory approval for the product in Mexico and introducing it to the new market.

Verity Co-Promotion Agreement

In April 2022, we entered into an agreement with Verity Pharmaceuticals International Limited (“Verity”) for the national co-promotion of Sancuso®.

Verity is a specialty pharmaceutical company that agreed to utilize its established oncology commercial organization to co-promote Sancuso throughout the United States.

Verity was to provide sales representation in the U.S.

market for an initial three-year term, with an option to extend for an additional two years.

In January 2023, we sent a 30-day notice of default to Verity due to failure of the parties to reach agreement regarding fundamental elements of the agreement, including targets and detailing obligations, among other items.

As a result, the agreement t erminated effective February 25, 2023.

We hope to work with Verity to seek a new arrangement for their continued co-promotion of Sancuso.

They are currently preparing their submission for the approval of Caldolor in their country.

Poly Co-Promotion Agreement

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We have agreements with 2R Investments, LLC and with Foxland Pharmaceuticals, Inc.

("Foxland") to package, distribute and promote an authorized generic form of our Kristalose product to physician targets that we do not cover.

(“Foxland”) to package, distribute and promote an unbranded generic form of our Kristalose product to physician targets that we do not cover.

We renewed our agreement with Foxland in 2022.

Nordic License Agreement

In July 2022, we entered into an amendment to our agreement with Nordic Pharma (“Nordic”) that addresses the responsibilities and financial arrangements regarding our license to Nordic’s methotrexate line of products for the U.S.

Our line of prefilled methotrexate syringes, marketed under the brand name RediTrex in the U.S., is covered by the license.

Based on the amendment, Nordic may assume responsibility for commercializing the methotrexate products in the U.S.

after June 30, 2023.

We will continue to distribute and support the RediTrex product line during a transition period until then.

In July 2022, we entered into an amendment to our agreement with Nordic Pharma (“Nordic”) that addressed the responsibilities and financial arrangements regarding our license to Nordic’s methotrexate line of products for the U.S.

Our line of prefilled methotrexate syringes, marketed under the brand name RediTrex in the U.S., was covered by the license.

As of July 1, 2023, Nordic has assumed responsibility for the product in the U.S.

Following the return of the license, Nordic will provide us with a royalty on their future sales of the products through April 2035.

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Cumberland transferred the marketing authorization associated with the RediTrex product line to Nordic.

Nordic returned the 180,000 shares we issued to them that were associated with the license and refunded the $1 million we paid them following the brand’s approval in the U.S.

They returned the 180,000 shares we issued to them that were associated with the license and refunded the $1 million we paid them following the brand’s approval in the U.S.

Nordic has also issued a credit note in favor of Cumberland in the amount of $1 million for the unpaid milestone payment due from us which was associated with our launch of the product line.

Clinigen Strategic Dissolution Agreement

We previously entered into an agreement with the Clinigen Group plc ("Clinigen"), an international specialty pharmaceutical and services company, to commercialize select Clinigen products in the U.S.

In May 2016, we announced an agreement with Clinigen to acquire an exclusive license and commercialize Ethyol ® in the U.S.

We then announced in January 2017, our second agreement with Clinigen to acquire an exclusive license and launch Totect ® in the U.S.

During May 2019, following a strategic review of our partners, products and organization, we entered into a dissolution agreement with Clinigen in which Cumberland returned the exclusive rights to commercialize Ethyol and Totect in the United States to Clinigen.

Under the final terms of the amended dissolution agreement we transitioned from our current arrangement with Clinigen effective December 31, 2019.

Under the terms of the agreement, Cumberland was no longer involved directly or indirectly with the distribution, marketing and promotion of either Ethyol or Totect or any competing products.

In exchange for the return of these product license rights and not competing with either product, we received $5 million in financial consideration paid over the two-years ending December 31, 2021.

CET University Collaboration Agreements

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CET has been able to help secure federal small business grant funding to support these various projects.

In addition, CET operates a Life Sciences Center in downtown Nashville to house its own research and development activities while providing laboratory space for other biomedical ventures.

CET has also established and manages the Nashville Life Sciences Center , which serves as an incubator for Middle Tennessee’s emerging biomedical industry.

The Life Sciences Center provides offices, laboratory space, and equipment to early-stage companies looking to develop their technologies and products.

We maintain the Cumberland Pharmaceuticals formulation and testing laboratory at the CET Life Sciences Center.

Nearly 30 life science companies exist today because of CET, including a vibrant group of current tenants at the Life Sciences Center as well as a growing number of successful graduates.

CLINICAL AND REGULATORY AFFAIRS

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Our team develops and manages our clinical trials, prepares regulatory submissions, manages ongoing product-related regulatory responsibilities and manages our medical information call center.

Team members have been responsible for devising the regulatory and clinical strategies for all our products as well as obtaining FDA approvals for Acetadote, Caldolor and RediTrex brands.

Team members have been responsible for devising the regulatory and clinical strategies for all our products as well as obtaining FDA approvals for Acetadote and Caldolor brands.

Clinical Development

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Our medical team provides in-house medical information support for our marketed products.

This includes interacting directly with healthcare professionals to address any product or medical inquiries through our medical information call center and medical science liaisons.

This includes interacting directly with health care professionals to address any product or medical inquiries through our medical information call center and medical science liaisons.

In addition to coordinating the call center, our clinical/regulatory group generates medical information letters, provides informational memos to our sales forces and assists with ongoing training for the sales forces.

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It addresses a range of Gram-positive bacterial pathogens, including those that are considered difficult-to-treat and multidrug-resistant.

In late 2019, we announced a publication in Infectious Diseases and Therapy , with study results showing numerically superior cure rates of telavancin compared to vancomycin within a subset of patients who were enrolled in Phase 3 ATTAIN trials and had hospital-acquired pneumonia caused by bacteria with low susceptibility to vancomycin.

Additionally, an online publication in Drugs - Real World Outcomes , detailed the positive clinical outcomes that resulted from treating multiple infection types with Vibativ, including complicated skin infections, bone and joint infections, bacteremia and endocarditis, and lower respiratory tract infections.

In May 2020, Cumberland announced a new study published in Drugs - Real World Outcomes , detailing the positive clinical outcomes that resulted from treating patients with bacteremia or endocarditis with Vibativ.

This publication is a sub analysis of The Telavancin Observational Use Registry (TOUR™), a study conducted to record population characteristics, prescription information, and real-world clinical outcomes of patients with Gram-positive infections treated with Vibativ.

The analysis suggests Vibativ is a promising and viable option for patients with bacteremia or endocarditis, including those with MRSA or another S.

In October 2023, Cumberland announced a new study published in Antimicrobial Agents and Chemotherapy detailing the results of the first clinical study investigating the safety and pharmacokinetics of our Vibativ (telavancin) product in children 2 to 17 years of age.

The study found a single 10 mg/kg dose of Vibativ was safe with no serious adverse events or renal concerns.

Drug exposure to Vibativ was lower in children compared with the same body weight-based dosing in adults.

The study suggests Vibativ is a safe and viable option for pediatric patients ages 2 to 17 who require systemic antibiotics for the treatment of a known or suspected bacterial infection, including those with MRSA or another S.

aureus pathogen.

Additionally, in May 2020, we announced the publication of two studies confirming the continued in vitro potency of telavancin.

Both publications were part of continued surveillance of telavancin activity since 2011.

The first publication tested a global collection of 24,408 Gram-positive clinical isolates, and the second publication tested a U.S.

collection of 15,882 S.

aureus isolates.

Both studies documented the sustained in vitro antimicrobial activity and spectrum of telavancin—many years after its clinical approval—against Gram-positive clinical isolates collected worldwide over seven years, from 2011 through 2017.

Caldolor Clinical Manuscripts

In July 2020, we announced a study published in the Journal of Orthopedic Trauma , evaluating the efficacy of Caldolor administration in the management of acute pain in orthopedic trauma patients.

The study also measured Caldolor’s ability in minimizing opioid use.

This single-center, randomized, double-blind, placebo-controlled study found that Caldolor (ibuprofen) Injection reduced the quantity of opioids required to manage pain after a traumatic injury with fracture.

In addition, the time to first narcotic medication was longer in the Caldolor group than with hospital standard of care.

Pain was also managed better in the Caldolor group compared to standard of care narcotics.

Additionally, in August 2020, we announced the results of a review of nine clinical studies evaluating Caldolor.

The comprehensive review was published in the journal Clinical Therapeutics and involved 1,062 adult patients, with 757 receiving Caldolor and 305 receiving placebo or a comparator medication.

The data noted that the use of Caldolor improved post-surgery recovery, decreased surgical stress, and reduced the use of opioids and over-the-counter medication.

The study determined that patients given Caldolor experienced less postoperative pain and decreased opioid use.

Study authors also concluded that the rapid administration and preemptive use of Caldolor should be considered in Enhanced Recovery After Surgery protocols for the management of postoperative pain including that of traumatic origin.

Caldolor Newborn Study

We previously received FDA approval for the use of Caldolor in pediatric patients six months of age and older.

Caldolor Newborn Study and Clinical Manuscripts

We previously received FDA approval for the use of Caldolor in pediatric patients 6 months of age and older.

Caldolor is the first and only injectable NSAID approved for use in children.

We then initiated a study to collect data on the use of Caldolor in children ranging in age from birth up to six months of age.

We then initiated a study to collect data on the use of Caldolor in children ranging in age from birth up to 6 months of age.

Enrollment in that multi-center study was completed in 2019, and topline results were announced in 2020, indicating that Caldolor was well tolerated in this patient population, with no safety concerns noted.

Renal Colic Study

During 2021, we report results from a clinical trial studying the comparison of intravenous ibuprofen with injectable ketorolac in renal colic pain management demonstrated that ibuprofen is the more rapid-acting drug in controlling pain caused by kidney stones.

The study also indicated that the complete relief from pain with ibuprofen was twice as much as that of ketorolac.

The findings build upon a body of medical evidence supporting the use of our Caldolor product for the treatment of patient pain.

Hyponatremia Publication

During 2021 we also reported on The Health Outcome Predictive Evaluation (“HOPE”) COVID-19 Registry Analysis.

It was an international study of over 4,000 patients published in November 2020, found that patients hospitalized with COVID-19 had a high risk of developing hyponatremia.

These COVID-19 patients also had a higher incidence of mortality due to their hyponatremia.

The study results support the use of an intravenous vaptan to treat hyponatremia in critically ill patients afflicted with COVID-19.

Hyponatremia, an imbalance of serum sodium to body water, is the most common electrolyte disorder among hospitalized patients.

Our Vaprisol product is one of two branded prescription products indicated for the treatment of hyponatremia, and the only intravenously administered branded treatment.

Vaprisol has a proven day-1 response rate to normalize serum sodium levels in hyponatremic patients and move them out of the Intensive Care Unit as efficiently as possible.

In May 2023, we announced the FDA approval of Caldolor in pediatric patients 3 to 6 months of age.

With this newly approved labeling, Caldolor is the only non-opioid injectable product approved to treat pain in infants that is delivered through injection.

Additionally, in June 2023, we shared the positive results from a clinical study investigating the safety and pharmacokinetics of Caldolor in newborns, published in the journal Pediatric Drugs .

The clinical study evaluated the safety and drug exposure profile of Caldolor in 24 hospitalized infants between the ages of 1 and 6 months who required treatment for pain or fever.

Of the 24 patients included in the study, three were under 3 months of age, and the remaining 21 patients were 3 to 6 months of age.

Twenty patients received a single dose, and four patients received multiple doses.

In this study, single and multiple 10 mg/kg doses of Caldolor were reported safe, with no drug-related adverse events or renal concerns.

Drug exposure following a single dose of Caldolor in infants 1 to 6 months of age was similar to what was previously reported in older children.

The results of this study support the growing body of evidence that demonstrates Caldolor is a safe therapeutic option available to practitioners for the treatment of fever and pain in infants, children and adults.

Ifetroban Phase II Studies

We have been evaluating our ifetroban product candidate in a series of clinical studies.

We have three Phase II clinical programs underway evaluating our ifetroban product candidate in 1) Aspirin-Exacerbated Respiratory Disease, a severe form of asthma, 2) Systemic Sclerosis or scleroderma, a debilitating autoimmune disorder characterized by diffuse fibrosis of the skin and internal organs and 3) patients with cardiomyopathy associated with Duchenne Muscular Dystrophy , a rare, fatal, genetic neuromuscular disease results in deterioration of the skeletal, heart and lung muscles.

common form of progressive fibrosing interstitial lung disease.

Investigational new study applications have been cleared by the FDA enabling us to launch clinical studies in each of these areas.

We have also completed two pilot Phase II studies involving 1) patients suffering from Hepatorenal Syndrome, a life-threatening condition involving liver and kidney failure and 2) patients with Portal Hypertension associated with chronic liver disease.

There were no significant safety issues identified with the use of ifetroban in these patients.

Additional pilot studies of ifetroban are underway, including several investigator-initiated trials.

Enrollment in our clinical studies was interrupted during 2021 and 2020 due to the COVID-19 pandemic.

In 2022, many of our clinical study sites have reopened and resumed screening of patients for potential enrollment into our studies.

We are awaiting results from the studies underway before deciding on the best development path for the registration of ifetroban, our first new chemical entity.

New Hospital Product Candidate Study

Cumberland was responsible for the formulation, development and FDA approval of both Acetadote and Caldolor.

Our Medical Advisory Board has helped us identify additional opportunities that address unmet or poorly met medical needs.

As a result, Cumberland has successfully designed, formulated and completed preclinical studies for a cholesterol reducing agent for use in the hospital setting.

We previously completed a Phase I study which defined the pharmacokinetic properties and provided a favorable safety profile for this new product candidate.

The study results and a proposed clinical development plan were discussed with the FDA.

A Phase II study has been initiated and patient enrollment completed.

We have completed the study report, filed it with the FDA and continue to consider next steps for this product development program.

Additional Testing Program

Cumberland entered into a non-clinical evaluation agreement, to test one of our products against bacterial strains utilizing the preclinical services program funded by the Division of Microbiology and Infectious Diseases (“DMID”), part of the National Institute of Allergy and Infectious Diseases (“NIAID”), an institute of the National Institutes of Health (“NIH”), which is part of the Department of Health and Human Services (“HHS”), an agency of the U.S.

Cumberland entered into a non-clinical evaluation agreement, to test one of our products against bacterial strains and subsequently, in vivo animal models utilizing the preclinical services program funded by the Division of Microbiology and Infectious Diseases (“DMID”), part of the National Institute of Allergy and Infectious Diseases (“NIAID”), an institute of the National Institutes of Health (“NIH”), which is part of the Department of Health and Human Services (“HHS”), an agency of the U.S.

The NIAID contractors completed these studies and prepared a manuscript for submission to a scientific journal for publication.

CORPORATE DEVELOPMENT

Cumberland Foundation

Cumberland Pharma Foundation

We have formed the Cumberland Pharma Foundation (the “Foundation”) to provide the ongoing philanthropic endeavors of Cumberland Pharmaceuticals Inc.

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The objective of the PAC is to support candidates and policies that are consistent with Cumberland’s mission of advancing patient care.

The PAC’s activities will be at the local, state and federal level and conducted in a bi-partisan manner.

The PAC’s activities are held at a local, state, and federal level and conducted in a bi-partisan manner.

The initial committee membership is comprised of Cumberland Pharmaceuticals employees.

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Omeclamox ® -Pak

The packager for Omeclamox-Pak encountered financial difficulties in 2020 due to the economic impact of COVID-19, and their operations are currently suspended.

The packager for Omeclamox-Pak encountered financial difficulties in 2020 due to the impact of COVID-19, and their operations are currently suspended.

As a result, we depleted our inventory of the product and notified the FDA that the product is currently unavailable.

We are awaiting resumption of those operations, while also exploring other alternatives to restart the product’s packaging.

In 2016, we entered into an agreement to acquire the exclusive U.S.

rights to an injectable methotrexate product line of pre-filled syringes.

In 2019, we received FDA approval for the product line.

Our licensor is responsible for providing us the packaged and labeled commercial supply of the product.

During 2022, we entered into two amendments to our agreement with Nordic Pharma.

Pursuant to the amendments, in exchange for financial consideration, Nordic may assume responsibility for distributing the methotrexate products in the U.S.

after June 30, 2023.

That facility is now under new ownership and new management.

We are awaiting resumption of their operations, while also exploring other alternatives to restart the product’s packaging.

With uncertain future cash flows, the Board of Directors approved the write-down of the intangible assets related to the product.

As part of the acquisition of Sancuso, we obtained an initial supply of finished goods inventory.

The agreement with the manufacturer of Sancuso was assigned to us and there were additional goods supplied to us during 2022.

The production is in the process of being moved to one of the manufacturer’s other facilities.

In late 2022, that new facility was approved by the FDA to manufacture and supply Sancuso.

The production was moved to one of the manufacturer’s other facilities.

During 2022, that new facility was approved by the FDA to manufacture and supply Sancuso.

We received supplies of the product from the new facility in 2023 and will begin shipping the Cumberland-packaged product during 2024.

As part of the acquisition of Vaprisol, we obtained a significant existing supply of raw material inventory.

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Our new manufacturing partner is working with the FDA to address several Form 483 and warning letter issues in a timely manner.

Meanwhile, we are working with them to support a special, interim supply of compounded product for critically ill patients, while awaiting the needed facility approval to relaunch Vaprisol.

We then expect to file for the approval to manufacture branded Vaprisol once all FDA issues at the new site are resolved.

Through our acquisition of Vibativ, we obtained a multi-year supply of raw material, work in process and finished goods inventory.

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We also require confidentiality agreements from entities to which we provide our confidential information or materials.

We developed a new formulation of Acetadote (acetylcysteine) Injection as part of a Phase IV commitment in response to a request by the FDA to evaluate the reduction of ethylene diamine tetraacetic acid ("EDTA") from the

product's formulation.

We developed a new formulation of Acetadote (acetylcysteine) injection as part of a Phase IV commitment in response to a request by the FDA to evaluate the reduction of ethylene diamine tetraacetic acid (“EDTA”) from the product’s formulation.

In April 2012, the USPTO issued U.S.

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Following its issuance, the 356 Acetadote Patent was listed in the FDA Orange Book.

The 356 Acetadote Patent is scheduled to expire in May 2026, which time period includes a 270-day patent term adjustment granted by the USPTO.

The 356 Acetadote Patent is scheduled to expire in May 2026, which includes a 270-day patent term adjustment granted by the USPTO.

Following the issuance of the 356 Acetadote Patent, we received separate Paragraph IV certification notices from InnoPharma, Inc.

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Patent number 7,608,282 (the “282 Sancuso Patent”) for Sancuso.

This patent was acquired in our December 2021 acquisition, that closed in January 2022, of certain product rights, intellectual property and related assets of Sancuso from Kyowa Kirin, Inc.

This patent was acquired in our December 2021 acquisition, which closed in January 2022.

The patent is of certain product rights, intellectual property and related assets of Sancuso from Kyowa Kirin, Inc.

The 282 Sancuso Patent is listed in the FDA Orange Book and is scheduled to expire in January 2025.

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Remaining Products

We have no issued patents for our Vaprisol, RediTrex, Omeclamox-Pak or Kristalose products.

We have no issued patents for our Vaprisol, Omeclamox-Pak or Kristalose products.

We have multiple granted patents relating to our ifetroban products and patent applications pending with the USPTO.

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Our products face competition from other branded products, generics, and alternate medical treatments.

Our task is to position each brand to feature its competitive advantages, implement a well thought out marketing plan and provide focused sales and other tactical support.

Our task is to position each brand to feature its competitive advantages, implement a well thought out marketing plan and provide focused sales, field based medical and other tactical support.

Acetadote is our injectable formulation of N-acetylcysteine (“ NAC”) for the treatment of acetaminophen overdose.

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• IV acetaminophen (brand name Ofirmev ®) , an injectable analgesic product is sold by Mallinckrodt plc, and there are also generic versions from different manufacturers available;

• Bupivacaine injectable suspension (brand name Exparel ® ), product sold by Pacira Pharmaceuticals, Inc., two additional bupivacaine products, Xaracoll and Posimir, were more recently approved.

• Bupivacaine and meloxicam extended release solution (brand name Zynrelef ® ), is a dual-acting anesthetic for postoperative pain sold by Heron Therapeutics;

• Oliceridine injection (brand name Olinvyk ® ), is an opioid agonist, a new chemical entity in the acute surgical postoperative pain market, sold by Trevena, Inc.;

• Bupivacaine injectable suspension (brand name Exparel ® ), product sold by Pacira Pharmaceuticals, Inc., along with two additional bupivacaine products, Xaracoll and Posimir,which were more recently approved;

• Acetaminophen and ibuprofen combination injection (brand name Combogesic ® ), is a combination of acetaminophen and ibuprofen approved by the U.S.

FDA in October 2023, and is sold by Hikma Pharmaceuticals PLC.

We are aware of other product candidates in development to treat acute pain including injectable NSAIDs, novel opioids, new formulations of existing therapies and extended release anesthetics.

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other than Caldolor and Ofirmev.

There are, however, numerous drugs available to physicians to reduce fevers in hospital settings via oral administration to the patient, including ibuprofen, acetaminophen, and aspirin.

There are, however, numerous drugs available to physicians to reduce fevers in hospital settings via oral and rectal administration to the patient, including ibuprofen, acetaminophen and aspirin.

These drugs are manufactured by numerous pharmaceutical companies.

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• Lubiproston (brand name Amitiza ® ), an oral product indicated for the treatment of chronic idiopathic constipation, irritable bowel syndrome with constipation in adults, is manufactured and sold by Mallinckrodt Pharmaceuticals.

• Naloxegol (brand name Movantik ® ), an oral product indicated for the treatment of opioid-induced constipation in adults with chronic non-cancer pain and recently acquired by RedHill Biopharma in the first quarter of 2020.

• Naloxegol (brand name Movantik ® ), an oral product indicated for the treatment of opioid-induced constipation in adults with chronic non-cancer pain.

It was acquired by RedHill Biopharma in the first quarter of 2020.

• Linaclotide (brand name Linzess ® ), an oral product indicated for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation.

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• Generic and branded liquid lactulose products are marketed by a number of pharmaceutical companies.

• Lactitol for oral solution (brand name Pizensy), an oral, osmotic laxative indicated for the treatment of chronic idiopathic constipation and distributed by Braintree Laboratories, Inc.

was recently approved by the FDA.

• Lactitol for oral solution (brand name Pizensy ® ), an oral, osmotic laxative indicated for the treatment of chronic idiopathic constipation.

It is distributed by Braintree Laboratories, Inc.

and was recently approved by the FDA.

There are several hundred OTC products used to treat constipation marketed by numerous pharmaceutical and consumer health companies.

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MiraLax was converted to an OTC product in February 2007 and recently, the FDA rescinded the approval of the generic prescription polyethylene glycol 3350 products.

Omeclamox-Pak ®

Omeclamox-Pak is a branded prescription product used for the treatment of Helicobacter pylori (H.

pylori) infection and duodenal ulcer disease.

It combines three well-known and widely prescribed medications packaged in a daily dose pack for patient convenience:

omeprazole, clarithromycin, and amoxicillin.

The three individual components of Omeclamox-Pak are also available from other suppliers through three separate prescriptions.

While there are several competitor products, Omeclamox-Pak is one of the two actively marketed products for this condition.

In addition, compared to the competing products, Omeclamox-Pak has the lowest pill burden, fewest days of therapy and convenient twice daily dosing.

The prescription combination products, indicated for treatment of H.

pylori, which we believe are our primary competitors are:

• PrevPac ® , an oral product sold by Takeda Pharmaceutical Company.

There are also approved generic versions of PrevPac;

• Pylera ® , an oral product manufactured and sold by Allergan plc;

• Talicia ® , an oral product manufactured by RedHill Biopharma which was recently approved by the FDA.

RediTrex is methotrexate for subcutaneous administration in a unique syringe designed for ease of use, improved accuracy, and enhanced safety.

It is indicated for treatment of rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and severe, recalcitrant, or disabling psoriasis unresponsive to alternative treatments.

This market is highly competitive with drugs from several different therapeutic classes available for treatment.

Methotrexate is considered a standard of care especially when patients fail to respond adequately to low dose steroids or non-steroidal anti-inflammatory drugs (NSAIDs).

Methotrexate is available in multiple dose forms including oral, subcutaneous, and intra-venous.

Methotrexate may be used alone or in combination with drugs from other therapeutic classes to adequately control patient symptoms.

RediTrex competes with other dose forms and delivery systems for methotrexate including, oral tablets, conventional vial and syringe administration, and auto-injector pens.

Oral tablets and conventional vials are generic and available from many suppliers.

There are two auto-injector pen products available, Rasuvo and Otrexup.

RediTrex also competes with or may be used in combination with drugs from other therapeutic classes including, injectable biologics like Humira and Enbrel and oral JAK inhibitors like Xaljanz.

These newer agents are more expensive than the methotrexate products but benefit from significant promotion to patients and doctors.

Sancuso is the only transdermal patch FDA approved for the management of chemotherapy induced nausea and vomiting (“CINV”).

Each patch delivers up to 5 days of treatment with granisetron, a standard of care for CINV, through the skin.

Each patch delivers up to five days of treatment with granisetron, a standard of care for CINV, through the skin.

Recommended treatment suggests the patch be applied 24 to 48 hours prior to chemotherapy treatment and remain in place for five days.

While there are no other transdermal products available to treat CINV, there are a large number of generic and branded oral products as well as a limited number of injectables.

Cumberland considers the oral branded products to be the most important competition including Akynzeo, Emend Oral, Varubi, Zuplenz, and Kytril.

While there are no other transdermal products available to treat CINV, there is a large number of generic and branded oral products as well as a limited number of injectables.

Cumberland considers the oral branded products to be the most important competition including Akynzeo;

Emend ® Oral (manufactured by Merck);

Varubi ® branded NK1 receptor antagonist sold by Tesaro Inc.

a division of GSK);

Zuplenz ® (a branded version of Ondansetron marketed by Par Pharmaceuticals, Inc.) and Kytril ® (a branded version of injectable granisetron hydrochloride manufactured by Roche Pharmaceuticals Inc.).

Vaprisol is a patented, prescription brand indicated to raise serum sodium levels in hospitalized patients with euvolemic and hypervolemic hyponatremia.

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It is one of two branded prescription products indicated for the treatment of hyponatremia, and the first and only intravenously administered branded treatment.

The other competing product is Samsca, an oral product sold by Otsuka Pharmaceutical Company.

The other competing product is Samsca ® (an oral tolvaptan product sold by Otsuka Pharmaceutical Company).

There are also several generic versions of tolvaptan sold by other companies.

Vibativ is a potent, once-daily, injectable antibiotic for the treatment of certain gram-positive infections.

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• Oritavancin (brand name Orbactiv ® ), an injectable antibiotic manufactured and sold by Melinta

We are aware of a number of other novel antibiotics which are currently in development.

We are also aware of a number of other novel antibiotics that are currently in development.

Antibiotic drug selection is based both on an empiric and susceptibility proven basis.

In the hospital setting, cost is an important factor which favors the use of generic agents as long as they are effective.

In the hospital setting, cost is an important factor which favors the use of generic agents if they are effective.

Newer agents are often reserved for two reasons:

they are valuable in the treatment of patients that fail to respond to generics and it is considered good practice to conserve the use of these agents to reduce the risk of resistance.

they are valuable in the treatment of patients that fail to respond to generics and it is considered good practice to conserve the use of these agents to reduce the risk of resistance.antimicrobial resistance, which is considered a global public health threat by the Center for Disease Control and Prevention (“CDC”).

GOVERNMENT REGULATION

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Failure to comply with applicable U.S.

requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to approve pending New Drug Application ("NDAs") or biologics license applications, ("BLAs"), warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties, and criminal prosecution.

requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to approve pending New Drug Applications (“NDAs”) or biologics license applications, (“BLAs”), warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties, and criminal prosecution.

We, our manufacturers and contract research organizations may also be subject to regulations under other federal, state and local laws, including the Occupational Safety and Health Act, (“OSHA”), the Resource Conservation and Recovery Act, the Clean Air Act and import, export and customs regulations as well as the laws and regulations of other countries.

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The FDA is a regulatory agency within the Department of Health and Human Services.

A key responsibility is to regulate the safety and effectiveness of drugs sold in the United States.

The FDA manages this responsibility into two phases:

pre-approval (premarket) and post approval (post market).

One of their key responsibilities is to regulate the safety and effectiveness of drugs sold in the United States.

The FDA manages this responsibility in two phases:

pre-approval (pre-market) and post approval (post-market).

The FDA reviews manufacturers' applications to market drugs in the United States;

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First, scientists work in the laboratory to discover and develop a new compound.

Next, basic questions on safety are answered by nonclinical testing with animals and then, a drug or biotechnology company develops a prototype drug.

That company must seek clearance from the FDA by way of an Investigational New Drug ("IND") application to test the product with human subjects.

Next, basic safety questions are answered by nonclinical testing with animals and then, a drug or biotechnology company develops a prototype drug.

That company must seek clearance from the FDA by way of an IND application to test the product with human subjects.

Those tests, called clinical trials, are carried out sequentially in Phase I, II, and III studies, which involve increasing numbers of subjects.

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The FDA may order the partial, temporary or permanent discontinuation of a clinical trial at any time or impose other sanctions if it believes that the clinical trial is not being conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical trial patients.

The institutional review board ("IRB"), or ethics committee (outside of the U.S.), of each clinical site generally must approve the clinical trial design and patient informed consent and may also require the clinical trial at that site to be halted, either temporarily or permanently, for failure to comply with the IRB's requirements or may impose other conditions.

The institutional review board ("IRB"), or ethics committee (outside of the U.S.), of each clinical site generally must approve the clinical trial design and patient informed consent and may also impose other conditions or require the clinical trial at that site to be halted, either temporarily or permanently, for failure to comply with the IRB's requirements.

The results of the nonclinical and clinical trials, together with detailed information on the manufacturing and composition of the product and proposed labeling, are submitted to the FDA in the form of an NDA for marketing approval.

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Once the NDA is validated and accepted for filing, the FDA begins an in-depth review of the NDA.

Under policies agreed to by the FDA under the Prescription Drug User Fee Act, or PDUFA (currently PDUFA VI - effective October 1, 2017), the FDA has a target timeline of 10 months in which to complete its initial review of a standard NDA and respond to the applicant.

The review process and the PDUFA goal date may be extended by two months to address deficiencies, or by three months if the FDA requests or the NDA sponsor otherwise provides additional information or clarification regarding information already provided in the submission at any time during the review clock period.

Under policies agreed to by the FDA under the Prescription Drug User Fee Act, or PDUFA (currently PDUFA VII - effective September 30, 2022), the FDA has a target timeline of 10 months in which to complete its initial review of a standard NDA and respond to the applicant.

The review process and the PDUFA goal date may be extended by two months to address deficiencies, or by three months if the FDA requests or if the NDA sponsor otherwise provides additional information or clarification regarding information already provided in the submission at any time during the review clock period.

If the FDA’s evaluations of the NDA and the clinical and manufacturing procedures and facilities are favorable and meet all regulations, the FDA will issue an approval letter.

Priority review is reserved for drugs that represent a “significant improvement in safety or efficacy” over existing treatments and FDA endeavors to complete these reviews in six months.

Priority review is reserved for drugs that represent a “significant improvement in safety or efficacy” over existing treatments.

The FDA endeavors to complete priority reviews in six months.

If the NDA meets with FDA approval, a letter will be sent out indicating approval and final labeling recommendations.

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An approval letter authorizes commercial marketing of the drug for the proposed indication(s) under study.

While the FDA's PDUFA 2021 Performance Report showed a continued increase in the percentage of first-cycle approval letters for new molecular entities rising from 56% for FY 2009 to preliminary reports of 100% for FY 2021, we cannot be certain that timely first-cycle approvals will be maintained by the FDA.

While the FDA’s PDUFA 2021 Performance Report showed a continued increase in the percentage of first-cycle approval letters for new molecular entities rising from 56% for FY 2009 to 84% for FY 2023, we cannot be certain that timely first-cycle approvals will be maintained by the FDA.

While the time and cost of completing these steps and obtaining FDA approval can vary dramatically depending on the drug, it can take many years and cost millions of dollars for a novel drug.

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Any marketing exclusivity is independent of patent exclusivity.

We successfully secured FDA approvals for Acetadote in January 2004, for Caldolor in June 2009 and for RediTrex in 2019 pursuant to the 505(b)(2) pathway.

We successfully secured FDA approvals for Acetadote in January 2004 and for Caldolor in June 2009 pursuant to the 505(b)(2) pathway.

Orphan drug designation

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Section 505(j) abbreviated new drug applications

An abbreviated new drug application ("ANDA") is a type of NDA where approval of a generic drug is based on demonstrating comparability to an innovator drug product (the RLD or Reference Listed Drug).

Applications are "abbreviated" because they generally don't include preclinical and clinical data to establish safety and effectiveness.

An abbreviated new drug application (“ANDA”) is a type of NDA where approval of a generic drug is based on demonstrating comparability to an innovator drug product (the Reference Listed Drug, or RLD).

Applications are "abbreviated" because they generally do not include pre-clinical and clinical data to establish safety and effectiveness.

Generics must demonstrate that the product is bioequivalent (i.e., performs in the same manner and is comparable to the 'innovator' product in active ingredient, dosage form, strength, route of administration, labeling, quality, performance characteristics and intended use).

Abbreviated applications may be submitted for drug products that are the same as a listed drug and must be identical in active ingredient(s), form, strength, route of administration, and identical in conditions of use (non-exclusive uses).

Products are declared suitable based on a suitability petition to the FDA.

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The Hatch-Waxman Act

The Drug Price Competition and Patent Term Restoration Act, informally known as the "Hatch-Waxman Act", is a 1984 United States federal law which established the modern system of generic drugs.

Hatch-Waxman amended the Federal Food, Drug, and Cosmetic Act.

The Drug Price Competition and Patent Term Restoration Act, informally known as the “Hatch-Waxman Act”, is a 1984 United States federal law that established the modern system of generic drugs.

The Hatch-Waxman Act amended the Federal Food, Drug, and Cosmetic Act.

Section 505(j) 21 U.S.C.

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Section 505(j)(2)(A)(vii)(IV), the so-called Paragraph IV, allows 180-day exclusivity to companies that are the "first-to-file" an ANDA against holders of patents for branded counterparts.

These Hatch-Waxman amendments grant generic manufacturers the ability to mount a validity challenge without incurring the cost of entry or risking enormous damages flowing from any possible infringement.

Hatch-Waxman essentially redistributes the relative risk assessments and explains the flow of settlement funds and their magnitude.

Hatch-Waxman gives generics considerable leverage in patent litigation.

These Hatch-Waxman Act amendments grant generic manufacturers the ability to mount a validity challenge without incurring the cost of entry or risking enormous damages flowing from any possible infringement.

The Hatch-Waxman Act essentially redistributes the relative risk assessments and explains the flow of settlement funds and their magnitude.

The Hatch-Waxman Act gives generics considerable leverage in patent litigation.

Health care legislation

On March 23, 2010, President Obama signed into law the Patient Protection and Affordable Care Act, or PPACA.

On March 30, 2010, the Health Care and Education Reconciliation Act of 2010, or HCERA, was enacted into law, which modified the revenue provisions of the PPACA.

On March 23, 2010, former President Obama signed into law the Patient Protection and Affordable Care Act, (“PPACA”).

On March 30, 2010, the Health Care and Education Reconciliation Act of 2010 (“HCERA”), was enacted into law, which modified the revenue provisions of the PPACA.

The PPACA as amended by the HCERA constitutes the healthcare reform legislation.

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Physician Payments Sunshine Act:

The PPACA also includes provisions known as the Physician Payments Sunshine Act, or Sunshine Act, which requires manufacturers of pharmaceuticals and medical devices covered under Medicare and Medicaid to record any transfers of value to physicians and teaching hospitals and to report this data to the Centers for Medicare and Medicaid Services, or CMS, for aggregation and subsequent public disclosure.

The PPACA also includes provisions known as the Physician Payments Sunshine Act (“Sunshine Act”), which requires manufacturers of pharmaceuticals and medical devices covered under Medicare and Medicaid to record any transfers of value to physicians and teaching hospitals and to report this data to the Centers for Medicare and Medicaid Services (“CMS”), for aggregation and subsequent public disclosure.

Under the Sunshine Act, beginning August 1, 2013, we have collected data regarding reportable transfers of value and have reported such data to CMS.

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Under the Medicaid Drug Rebate program we currently are required to provide rebates for covered outpatient drugs that are dispensed to Medicaid beneficiaries.

In addition, we also are required to participate in the Public Health Service's 340B drug pricing program, which requires us to agree to charge no more than a designated ceiling price for covered outpatient drugs that are dispensed to community health clinics and other

entities that receive health services grants from the Public Health Service, as well as hospitals that serve a disproportionate share of low-income patients.

In addition, we also are required to participate in the Public Health Service’s 340B drug pricing program, which requires us to agree to

charge no more than a designated ceiling price for covered outpatient drugs that are dispensed to community health clinics and other entities that receive health services grants from the Public Health Service, as well as hospitals that serve a disproportionate share of low-income patients.

Product Serialization:

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DSCSA requires trading partners, including manufacturers, repackagers, wholesale distributors and dispensers to provide transaction information to subsequent purchasers for certain prescription drugs.

We have taken necessary steps to implement this program and are in compliance with all requirements by the November 2018 deadline.

We have taken necessary steps to implement this program and are in compliance with all requirements.

21 st Century Cures Act:

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Build Back Better Act and Other Proposed Legislation:

The Build Back Better Act ("BBBA") was introduced in the 117 th Congress and included provisions that were intended to lower the price of prescription drugs, including granting the Medicare program the authority to negotiate prescription drug prices and imposing tax penalties on drug manufacturers if the price of drugs increase too rapidly.

The Build Back Better Act (“BBBA”) was introduced in the 117 th Congress and included provisions that were intended to lower the price of prescription drugs, including granting the Medicare program the authority to negotiate prescription drug prices and imposing tax penalties on drug manufacturers if the price of drugs increases too rapidly.

Ultimately the BBBA was not enacted, however, future legislative initiatives are likely to include provisions targeted at containing costs in the prescription drug market.

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The federal health care program anti-kickback statute prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration to induce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any health care item or service reimbursable under Medicare, Medicaid or other federally financed health care programs.

This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other.

This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers and prescribers, purchasers or formulary managers.

Violations of the anti-kickback statute are punishable by imprisonment, criminal fines, civil monetary penalties and exclusion from participation in federal health care programs.

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In the United States, we and our collaborators are subject to numerous federal and state privacy and security laws and regulations, including the Health Insurance Portability and Accountability Act of 1996.

These laws include obligations related to protecting the privacy and security of health-related personal information, including information that we may obtain through the clinical trial process.

These laws include obligations related to protecting the privacy and security of health-related personal information, such as information that we may obtain through the clinical trial process.

In addition, similar laws and regulations exist in Europe and other jurisdictions, including the European Union’s General Data Protection Regulation.

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• The possible or assumed future results of operations, including the accuracy of our estimates regarding expenses, future revenues, capital requirements and needs for additional financing;

• Changes in national or regional economic conditions, including changes in interest rates and the availability and the cost of capital to us;

• The impact of a pandemic, epidemic or outbreak of a contagious disease, such as the novel coronavirus (COVID-19) pandemic, including any recurrence of the COVID-19 pandemic, the impact on our employees, the extent of the impact on overall demand for our key products and the impact on our suppliers, including any disruptions and inefficiencies in the supply chain for our products;

• The impact of macroeconomic conditions, including inflationary pressures, rising interest rates, general economic slowdown or a recession, changes in monetary policy, volatile market conditions, financial institution instability, as well as geopolitical instability and the ongoing conflicts outside the U.S., on our operations;

• Our competitive position and competitors, including the size and growth potential of the markets for our products and product candidates;

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and the retention of key scientific and management personnel;

• The impact on our business, financial condition and results of operations from the effects of a pandemic or the outbreak of an infectious disease in the United States and worldwide and resulting governmental and societal responses;

• Challenges to our patents and the introduction of generic versions of our products and product candidates, which could negatively impact our ability to commercialize and sell our products and product candidates and decrease sales a result of market exclusivity;

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

What changed 10-K

Item 1. Business