What changed in this filing

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Item 1. Business

2022-03-11 compared with 2021-03-12 · 406 added, 322 removed, 588 unchanged (55% of the section changed)

Cumberland Pharmaceuticals Inc.

(“Cumberland,” the “Company,” or as used in the context of “we,” “us,” or “our”), is a specialty pharmaceutical company focused on the acquisition, development and commercialization of branded prescription products.

Our primary target markets are hospital acute care, gastroenterology and rheumatology.

These medical specialties are characterized by relatively concentrated prescriber bases that we believe can be penetrated effectively by small, targeted sales forces.

Cumberland is dedicated to providing innovative products that improve the quality of care for patients and address poorly met medical needs.

We promote our approved products through our hospital and field sales forces in the United States and are establishing a network of international partners to register and provide our medicines to patients in their countries.

Our portfolio of FDA approved brands include:

We are dedicated to providing innovative products that improve the quality of care for patients and address poorly met medical needs.

Our primary target markets are hospital acute care, gastroenterology, rheumatology and oncology.

These medical specialties are characterized by relatively concentrated prescriber bases, that we believe can be served effectively by small, targeted sales forces.

We promote our approved products through our hospital, field and oncology sales divisions in the United States and are establishing a network of international partners to register and provide our medicines to patients in their countries.

Our portfolio of brands approved for marketing by the U.S.

Food and Drug Administration (“FDA”) includes:

• Acetadote ® ( acetylcysteine ) injection, for the treatment of acetaminophen poisoning;

• Caldolor ® ( ibuprofen ) injection, for the treatment of pain and fever;

• Kristalose ® ( lactulose ) for Oral Solution, a prescription laxative, for the treatment of chronic and acute constipation;

• Kristalose ® ( lactulose ) for oral solution, a prescription laxative, for the treatment of constipation;

• Omeclamox ® -Pak , ( omeprazole, clarithromycin, amoxicillin ) for the treatment of Helicobacter pylori ( H.

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 system, for the prevention of nausea and vomiting in patients receiving certain types of chemotherapy treatment;

• Vaprisol ® ( conivaptan ) injection, to raise serum sodium levels in hospitalized patients with euvolemic and hypervolemic hyponatremia;

• 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.

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

In addition to these commercial brands, we have Phase II clinical programs underway evaluating our ifetroban product candidates in patients with cardiomyopathy associated with Duchenne Muscular Dystrophy (“DMD”), a degenerative disease, Systemic Sclerosis (“SSc”), a deadly autoimmune condition, and Aspirin-Exacerbated Respiratory Disease ("AERD"), a severe form of asthma.

Cumberland has built core competencies in both product development and commercial capabilities.

In addition to these commercial brands, we have Phase II clinical programs underway evaluating our ifetroban product candidates 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.

Cumberland has built core competencies in both the development and commercialization of pharmaceutical products.

We have established the capabilities needed to acquire, develop and commercialize branded pharmaceuticals in the U.S.

and believe we can leverage this existing infrastructure to support our expected growth.

Our management team consists of pharmaceutical industry veterans experienced in business development, product development, regulatory, manufacturing, sales, marketing and finance.

Our management team consists of pharmaceutical industry veterans with experience in business development, product development, regulatory, manufacturing, sales, marketing and finance.

Our business development team identifies, evaluates, and negotiates product acquisition, licensing and co- promotion agreements.

Our product development team creates proprietary product formulations, manages our clinical studies, prepares all regulatory submissions and staffs our medical call center.

Our quality and manufacturing professionals oversee the manufacture, release and shipment of our products.

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

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

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

Through our international partners, we are working to bring our medicines to patients in their countries.

We also look for opportunities to expand our products into additional patient populations through clinical trials, through new presentations, and through our support for select, investigator-initiated studies.

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 and unmet 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 progress promising, new product candidates, which Cumberland has the opportunity to further develop and commercialize.

Our product development team creates proprietary formulations, manages our clinical studies, prepares our FDA submissions and staffs our medical call center.

Our quality and manufacturing professionals oversee the manufacturing, release and shipment of our products.

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, a respiratory illness.

The Company has 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 has 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.

Several of our brands were negatively impacted by the lockdowns and postponement of physician office visits and elective procedures.

However, we are fortunate to have a diversified product portfolio that includes other brands that have delivered a strong performance during the pandemic.

Despite the challenges of operating during a pandemic, Cumberland has remained committed to our mission of providing innovative products that improve the quality of care for patients and address poorly met medical needs.

We continued to build our portfolio of innovative and differentiated products through a multifaceted strategy that includes the development of new candidates and acquisition of established brands.

Our resulting, diversified product line has enabled us to weather external challenges, while our team has remained responsive to the evolving medical market.

We are prepared for and look forward to future opportunities to carry out our mission.

Overall, we have been able to continue the delivery of our products while addressing the interests of our shareholders, employees, partners and community.

In July 2021, we released our second annual Sustainability Report (the “2020 Sustainability Report”), which details Cumberland’s activities pertaining to our environmental, social and governance (“ESG”) matters.

After issuing our inaugural ESG Report the prior year (the “2019 Sustainability Report”), we 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 2020 Sustainability Report notes that during that year we provided nearly 2.5 million patient doses of our products, safely disposed of over 4,000 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 2020 Sustainability Report also highlights our investment in our employees through our continuing education programs, employee development initiatives and employee recognition awards.

We reported that women represented 46% of Cumberland’s workforce – and 18% of our employees were minorities.

We were incorporated in 1999 and have been headquartered in Nashville, Tennessee since inception.

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Our website address is www.cumberlandpharma.com .

We make available through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and all material press releases, other filings and amendments to those reports as soon as reasonably practicable after their filing with the U.S.

Our Annual Reports (on Form 10-K), Quarterly Reports (on Form 10-Q), Current Reports (on Form 8-K) and all material press releases are available on our website as soon as reasonably practicable after their filing with the U.S.

Securities and Exchange Commission, (“SEC”).

These filings are also available to the public at www.sec.gov.

COVID-19 Pandemic

In March 2020, the U.S.

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

The Company managed through the COVID-19 pandemic during 2020, continuing to operate our business - keeping facilities open and our organization intact.

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 headwinds affecting other companies that rely on hospital admissions and patient visits to drive revenue.

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

During 2020, we carefully monitored our supply chain during the pandemic including the flow of raw materials into the plants that manufacture our products as well as the batches of finished product emerging from those facilities.

Several of our brands were negatively impacted by the lockdowns and postponement of physician office visits and elective procedures.

However, we are fortunate to have a diversified product portfolio, with other brands delivering a strong performance.

Our key products include:

Products Indication Status

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pylori Infection and Related Duodenal Ulcer Disease Marketed

Arthritis and Psoriasis Marketed

Nausea and Vomiting Associated with Chemotherapy Marketed

Euvolemic and Hypervolemic Hyponatremia Marketed

Serious Bacterial Infections Marketed

Arthritis and psoriasis Approved

Acetadote is an intravenous formulation of N-acetylcysteine, indicated for the treatment of the liver toxicity associated with acetaminophen poisoning.

Acetadote has been available in the United States since Cumberland's 2004 introduction of the product through our hospital sales force.

Acetadote is an intravenous formulation of N-acetylcysteine, indicated for the treatment of liver toxicity associated with acetaminophen poisoning.

Cumberland developed and obtained U.S.

FDA approval for Acetadote, and then introduced the product through our hospital sales force.

Acetadote is typically used in hospital emergency departments to prevent or lessen potential liver damage resulting from an overdose of acetaminophen, a common ingredient in many over-the-counter and prescription pain relieving and fever-reducing products.

Acetaminophen overdose continues to be a leading cause of poisonings reported by hospital emergency departments in the United States, and Acetadote has become a standard of care for treating this potentially life-threatening condition.

Acetaminophen overdose continues to be a leading cause of poisonings reported by hospital emergency departments in the U.S., and Acetadote has become a standard of care for treating this potentially life-threatening condition.

Acetadote received U.S.

Food and Drug Administration ("FDA") approval as an orphan drug, which provided seven years of marketing exclusivity from the date of approval.

FDA approval as an orphan drug, which provided seven years of marketing exclusivity from the date of approval.

That exclusivity has since expired.

In connection with the FDA's approval of Acetadote, we committed to certain post-marketing activities for the product.

Completion of our first Phase IV commitment resulted in the FDA's approval of expanded labeling for the product for use in pediatric patients.

Completion of our second Phase IV commitment resulted in further revised labeling for the product with FDA approval of additional safety data in 2008.

Completion of our third and final Phase IV commitment in 2010 culminated in the FDA’s approval of a new formulation for the product.

Completion of our second Phase IV commitment resulted in further revised labeling for the product with FDA approval of additional safety data.

Completion of our third and final Phase IV commitment culminated in the FDA’s approval of a new formulation for the product.

The next generation formulation, contains no ethylene diamine tetracetic acid (“EDTA”) or other stabilization agent, chelating agent or preservative.

In early 2011, Cumberland introduced this new Acetadote formulation replacing the original form of the product which we no longer manufacture.

In June 2013, the FDA approved updated labeling for Acetadote revising the product's indication and providing new dosing guidance for specific patient populations.

As a result, dosing guidance is now included for patients weighing over 100 kg, and new language has been added to alert health care providers that, in certain clinical situations, therapy should be extended for some patients.

Beginning in 2012, the United States Patent and Trademark Office (the "USPTO") issued us a series of patents associated with our Acetadote product.

Cumberland introduced this new Acetadote formulation replacing the original form of the product which we no longer manufacture.

The FDA subsequently approved updated labeling for Acetadote revising the product's indication and providing new dosing guidance for specific patient populations.

As a result, dosing guidance is now included for patients weighing over 100 kg, and new language was added to alert health care providers that, in certain clinical situations, therapy should be extended for some patients.

The United States Patent and Trademark Office (the “USPTO”) issued us a series of patents associated with our Acetadote product.

These patents are discussed in Part I, Item I – “ Business - Trademarks and Patents ” - of this Form 10-K.

On November 8, 2012, we learned that the FDA approved an abbreviated new drug application (ANDA) filed by InnoPharma, Inc.

and referencing Acetadote.

That product, with the old formulation containing EDTA, was subsequently introduced by APP, a division of Fresenius Kabi USA, at the end of 2012.

In early 2013, we entered into an agreement with Perrigo Company resulting in the distribution of our Authorized Generic acetylcysteine injection (our "Authorized Generic") product.

Both Acetadote and our Authorized Generic utilize the new, EDTA-free formulation which accounted for continued significant market share during 2020.

In November 2015, an Illinois judge issued a final ruling in favor of Cumberland Pharmaceuticals Inc.

The FDA has approved several abbreviated new drug applications (ANDA) filed by various generics companies referencing Acetadote.

Those products all possess the old formulation containing EDTA.

We entered into an agreement with Perrigo Company resulting in the distribution of our Authorized Generic acetylcysteine injection (our “Authorized Generic”) product.

Both Acetadote and our Authorized Generic utilize the new, EDTA-free formulation.

An Illinois judge issued a final ruling in favor of Cumberland Pharmaceuticals Inc.

in a patent case associated with Acetadote.

By ruling in Cumberland's favor, the court upheld the validity of the patent which encompasses our EDTA-Free formulation and has a term until August 2025.

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.

On January 26, 2017, an Appeals Court affirmed the District Court ruling in the Company's favor upholding Cumberland's Acetadote patent and expressly rejected the validity challenge.

During 2020 we continued to distribute our Acetadote brand and, through Perrigo Company, our Authorized Generic product.

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

During 2021, we continued to distribute our Acetadote brand, however our Authorized Generic product is now distributed through Padagis US LLC (formerly a division of Perrigo Company).

Caldolor, our intravenous formulation of ibuprofen, was the first injectable product approved in the U.S.

for the treatment of both pain and fever.

We conducted a series of clinical studies in over nine hundred adult patients to develop the data to support our FDA submission for the product's registration.

The FDA approved Caldolor for marketing in the United States in 2009 following a priority review.

We conducted a series of clinical studies in over 900 adult patients to develop the data to support our FDA submission for the product's registration.

Following a priority review, the FDA approved Caldolor for marketing in the U.S..

A non-steroidal anti-inflammatory drug (“NSAID”), the product was indicated for use in adults as a sole treatment for the management of mild to moderate pain and for the management of moderate to severe pain as an adjunct to opioid analgesics.

It was also the first FDA approved intravenous therapy for treating fever.

In late 2009, we launched Caldolor and stocked the product at major wholesalers serving hospitals nationwide.

We initially worked to establish a core group of medical facilities approving and purchasing the product and then focused on building more sales volume and treating a broader range of patients within those stocked facilities.

We promote Caldolor in the United States through our dedicated hospital sales force.

We then launched Caldolor and continue to promote the product in the U.S.

through our hospital sales force.

We completed a series of Phase IV studies to gather additional data to support our Caldolor product.

Those clinical trials involved another 1,000 patients, adult and pediatric patients.

Those clinical trials involved another 1,000 adult and pediatric patients.

These studies included data on a shortened infusion time and pre-surgical administration of the product.

To address our Phase IV commitment to the FDA, these studies also included evaluation of the product for the reduction of fever in hospitalized children and the treatment of pain in children undergoing tonsillectomy surgeries.

In 2015 we received FDA approval for the use of Caldolor in pediatric patients six months of age and older.

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 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 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.

In April 2018, the FDA determined that the application was complete and notified us of their acceptance of the submission for review.

There were then a number of communications with questions addressed through multiple amendments that were submitted to the application.

In January 2019, the FDA approved the application for our next generation Caldolor product.

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.

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

In April 2019, we began initial shipments of this next generation Caldolor product to select customers.

During the third and fourth quarters of 2019, there was a growing demand for the new product from these select accounts.

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 postponement of elective surgeries.

Nonetheless, we do expect an improved performance of the product after the pandemic abates as more accounts gain access to the new presentation.

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

Nonetheless, we expect an improved performance of the product after the pandemic abates and more accounts gain access to the new presentation.

During 2021, we distributed both the vial and the ready-to-use premixed bag presentations of Caldolor.

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

During our clinical studies we found that the product delivered its best results when dosed prior to surgery, reducing both patient pain as well as their need for opiates.

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

An innovative, dry powder crystalline formulation of lactulose, Kristalose is designed to enhance patient acceptance and compliance.

Kristalose is the only prescription laxative available in pre-measured powder packets.

Kristalose dissolves easily in four ounces of water, offering patients a virtually taste-free, grit-free and essentially calorie-free alternative to lactulose syrups.

We conducted a preference study which indicated that seventy-seven percent of patients surveyed prefer the taste, consistency and portability of Kristalose over similar products in syrup forms.

We acquired exclusive U.S.

commercialization rights to Kristalose in 2006, assembled a dedicated field sales force and re-launched it in September 2006 as a Cumberland brand.

It is the only prescription laxative available in pre-measured powder packets.

Kristalose dissolves easily in 4 ounces of water, offering patients a virtually taste-free, grit-free and essentially calorie-free alternative to lactulose syrups.

We conducted a preference study which indicated that 77% of patients surveyed prefer the taste, consistency and portability of Kristalose over similar products in syrup forms.

We acquired the assets and exclusive rights to Kristalose through a series of transactions, then assembled a dedicated field sales force which re-launched the product as a Cumberland brand.

We directed our sales efforts to physicians who are the most prolific writers of prescription laxatives, including gastroenterologists and internists.

We supplemented this personal promotion with telemarketing campaigns to expand our reach and support of the product.

In late 2011, through a series of transactions, we entered into an agreement to acquire assets associated with the Kristalose brand including the Kristalose trademark and the FDA registration.

Using preference data as a cornerstone of our marketing efforts, we repositioned the brand in early 2014.

The marketing strategy included an enhanced patient coupon program and expanded managed care coverage for the product.

We added a co-promotion partner to provide support for the brand in 2017.

Poly Pharmaceuticals is promoting Kristalose to physician targets not covered by our field sales forces.

In 2018, we added another partner, Foxland Pharmaceuticals, Inc., who is repackaging Kristalose and featuring it with additional new physician targets.

Using preference data as a cornerstone of our marketing efforts, we repositioned the brand, enhancing patient affordability through a coupon program and expanded managed care coverage for the product.

We added a co-promotion partner, Poly Pharmaceuticals, who is promoting Kristalose to physician targets not covered by our field sales forces.

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

During 2021 we continued to support Kristalose through our field sales force as well as our partnerships with Poly Pharmaceuticals and Foxland Pharmaceuticals, Inc.

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Omeclamox-Pak was the first FDA approved triple therapy combination medication to contain omeprazole as the proton pump inhibitor, which works to decrease the amount of acid the stomach produces.

Clarithromycin and amoxicillin are both antibiotic agents which hinder the growth of the H.

Clarithromycin and amoxicillin are both antibiotic agents that hinder the growth of the H.

pylori bacteria.

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The medications are packaged together on convenient daily dosing cards, making it simple to follow the twice a day dosing before meals.

While there are competing combination products, Omeclamox-Pak is one of the few actively marketed brands for this condition.

In addition, compared to the competitors, Omeclamox-Pak involves the lowest pill burden and fewest days of therapy.

Our involvement with Omeclamox-Pak began in October 2013, through a co-promotion agreement with Pernix Therapeutics ("Pernix").

In November 2015, Cumberland entered into an exclusive license and supply agreement with Gastro-Entero Logic, LLC (“GEL”), assumed full commercial responsibility for Omeclamox-Pak in the United States, and concluded our agreements with Pernix.

Cumberland became responsible for the distribution, national accounts and all sales promotion of Omeclamox-Pak under the GEL agreement.

In December 2018, we completed an agreement with GEL to acquire all remaining assets associated with Omeclamox-Pak including the product’s FDA approval as well as the domestic and international trademarks.

The closing of this transaction ended Cumberland’s payments of royalties and manufacturing fees to GEL, and we assumed responsibility for the maintenance of the product’s FDA approval and for the oversight of the product’s manufacturing and packaging.

Our field sales force has promoted Omeclamox-Pak to the gastroenterology market segment, which accounts for the largest component of the prescriber base for this product.

We supplemented this personal promotion through telemarketing campaigns to expand the support and use of the product.

We have also established a series of contracts to provide managed care coverage for Omeclamox-Pak.

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 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.

We have notified the FDA that the product is currently not available.

In early 2014, we entered into an agreement with Astellas Pharma US, Inc.

("Astellas") to acquire Vaprisol, including certain product rights, intellectual property and related assets.

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

The product was developed and registered by Astellas.

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

RediTrex is a new 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.

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

assets and rights to Sancuso ® (granisetron transdermal system), an FDA-approved oncology supportive care medicine.

This transaction closed in January 2022.

Sancuso ® is the first and only FDA-approved prescription patch for the prevention of nausea and vomiting in patients receiving certain types of chemotherapy treatment for their cancer.

The active drug in Sancuso ® , granisetron, slowly dissolves in the thin layer of adhesive that sticks to the patient’s skin and is released into their bloodstream over several days, working continuously to prevent chemotherapy-induced nausea and vomiting (CINV).

It is applied 24 to 48 hours before receiving chemotherapy and can prevent CINV for up to five consecutive days.

Alternative oral treatments must be taken several times (day and night) to deliver the same therapeutic doses.

In early 2022 we assumed full commercial responsibility for the product in the U.S.

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

Kyowa Kirin will retain 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.

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.

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

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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.

Vaprisol is supported by our hospital sales division.

Demand for the product increased during the 2020 pandemic, and we worked to ensure availability of the product to hospitals and clinics during the health care crisis.

In November 2018, the Company announced an agreement with Theravance Biopharma ("Theravance") to acquire the Vibativ assets from Theravance and assume global responsibility for the brand including the related marketing, distribution, manufacturing and regulatory activities.

Vibativ is a patented, FDA approved injectable anti-infective for the treatment of certain serious bacterial infections including hospital-acquired and ventilator-associated bacterial pneumonia and complicated skin and skin structure infections.

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

Immediately after the closing, we initiated shipments of Vibativ, assumed responsibility for the supply chain and distribution of the product in the U.S.

and transitioned the brand's responsibilites from Theravance to Cumberland.

Vibativ is supported by our hospital sales division.

During 2020, demand for the product grew, and it was used to treat pneumonia resulting from secondary bacterial infections in hospitalized COVID-19 patients.

In November 2016, we announced an agreement with Nordic Group B.V.

to commercialize their methotrexate product line in the United States.

This new line of injectable products is designed for treating patients with arthritis and psoriasis.

Cumberland is responsible for the registration and commercialization of these products while Nordic will manage the product supply.

Nordic has registered and is selling their methotrexate products in several European countries.

During late 2018, we completed the submission and filed with the FDA a New Drug Application for our methotrexate products.

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

In November 2020, we provided initial shipments of RediTrex to select accounts and began preparing for a national launch in the second half of 2021, once product supplies are assured and market conditions return to normal.

Our development pipeline includes a series of product candidates in Phase II development.

During 2020, enrollment in our studies significantly slowed during the pandemic, due to trial suspensions and the decrease in eligible patient admissions to medical centers across the country.

We look forward to an improvement as the pandemic subsides and centers begin to reopen with a return of patients eligible for our trials.

Our clinical programs include the evaluation of ifetroban in the following areas:

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 transferred manufacturing of the product to a new manufacturing facility, and await the submission and FDA approval for the new facility before resuming shipments.

We are also exploring alternatives for providing an interim supply to the market while awaiting the needed approval.

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.

In early 2021 we introduced the Cumberland-packaged product, which is supported by our hospital sales force.

Vibativ is a patented, FDA-approved injectable anti-infective.

It is designed to treat serious infections due to Staphylococcus aureus (S.

aureus) and other Gram-positive bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA ).

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

Vibativ can serve as a potentially life-saving treatment in patients with hospital-acquired and ventilator-associated pneumonia resulting from infections including the flu and COVID-19.

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.

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

In comparison to vancomycin, Vibativ is 32 times more potent against MRSA strains when tested under in vitro conditions.

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

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 2021.

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

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.

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

Aspirin-Exacerbated Respiratory Disease ("AERD")

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

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

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

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

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approved pharmaceutical treatment for AERD.

We completed an initial Phase II clinical study to evaluate the safety and tolerability of Boxaban in AERD patients.

The multicenter study involved sixteen patients at several U.S.

medical centers led by the Scripps Research Institute.

Results indicated that Boxaban was well tolerated with no safety concerns noted in patients with a history of AERD.

In early 2017, the FDA cleared Cumberland’s IND application for the Company’s AERD clinical program.

Following this clearance, we initiated a follow-on multicenter Phase II efficacy study to evaluate the efficacy of Boxaban in seventy-six patients with symptomatic AERD.

Preclinical studies at Harvard revealed that ifetroban blocks all features of the asthma reaction triggered by aspirin highlighting the important role of TPr in AERD.

Our Harvard collaborators were awarded a $5 million National Institutes of Health grant to evaluate oral ifetroban in approximately 45 AERD patients undergoing aspirin desensitization in a phase II clinical trial.

Patient enrollment in this trial is well underway.

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 study is progressing with patient enrollment ongoing at multiple U.S.

Systemic Sclerosis ("SSc")

In April 2016, we announced the addition of Vasculan to our pipeline.

Through Cumberland's ifetroban program, Cumberland has initiated the clinical development of ifetroban oral capsules for the treatment of systemic sclerosis.

Systemic sclerosis ("SSc"), also called scleroderma, is a debilitating autoimmune disorder characterized by diffuse fibrosis of the skin and internal organs, as well as vascular dysfunction.

Preclinical studies have shown that ifetroban prevents and can restore cardiac function in a preclinical model of pulmonary arterial hypertension.

This disease has a high morbidity and the highest case-specific mortality of any rheumatic disorder with 50% of patients dying or developing major internal organ complications within 3 years of diagnosis.

Although several medications are used to treat the skin disease associated with SSc, there is no universally effective treatment to improve the function of affected internal organs such as the lungs, heart, and gastrointestinal tract.

The FDA has cleared our IND application to evaluate the safety and efficacy of Vasculan in patients with SSc.

As a result, we initiated a Phase II multicenter study in thirty-four SSc patients.

Next, we 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.

SSc has a high morbidity and the highest case-specific mortality of any rheumatic disorder with 50% of patients dying or developing major internal organ complications within three years of diagnosis.

Cardiac involvement associated with SSc is often underestimated due to its subtle and atypical presentation.

Despite the cardiovascular events associated with its elevated mortality at later stages of the disease, overt signs are suggestive of advance disease including myocardial or pericardial inflammation, heart failure and pulmonary arterial hypertension (PAH).

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 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 also 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")

On September 24, 2019, Cumberland announced an FDA Orphan Drug Grant funding for a new Phase II clinical program.

The Company has initiated the clinical development of ifetroban for the treatment of cardiomyopathy associated with Duchenne Muscular Dystrophy (“DMD”).

Based on preclinical findings, the FDA has cleared Cumberland’s application to study ifetroban in DMD patients, 7 years of age and older.

In addition, Cumberland has been awarded just over $1 million in funding from the FDA through their Orphan Drug Grant program to support this Phase II DMD clinical study.

It is the first DMD clinical study approved for FDA Orphan Product Development funding.

During 2020 the FDA awarded a supplemental grant in support of the Phase II study.

Other Clinical Programs

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.

Cardiomyopathy is the leading cause of death in DMD patients.

TPr and its ligand, isoprostanes, are found to have increased in DMD patients.

Preclinical studies by our Vanderbilt collaborators demonstrated TPr blockade by ifetroban prevented cardiac dysfunction and improved mortality in several animal models of muscular dystrophy.

These results published in the Journal of the American Heart Association suggest TPr activation contributes to DMD cardiomyopathy and blockade with ifetroban may serve as a novel therapeutic for DMD patients.

The FDA cleared Cumberland’s application to evaluate 12 months of oral ifetroban (Dyscorban) in a Phase II study entitled, A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study with an Open-Label Extension to Determine the Safety, Pharmacokinetics and Efficacy of Oral Ifetroban in Subjects with Duchenne Muscular Dystrophy .

With medical centers across the U.S.

screening patients, our clinical study is enrolling those with 48 ambulatory and non-ambulatory DMD, 7 years of age and older with stable cardiac function.

Cumberland was awarded just over $1 million in federal funding to support this clinical trial, which is the first DMD clinical study awarded FDA Orphan Product Development funding.

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.

Progressive Fibrosing Interstitial Lung diseases (“PF-ILDs”)

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.

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

We are awaiting further study results before deciding on the best path for approval for ifetroban, our first new chemical entity.

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

New Hospital Product Candidate

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

During 2017, we completed a Phase I study which defined the pharmacokinetic properties and provided a favorable safety profile for this new product candidate.

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 and patient enrollment completed.

We have completed the study report, filed it with the FDA and are now determining the next steps for this program.

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

We currently market seven FDA approved products for sale in the United States.

Through our international partners, we are working to bring our products to patients in their countries.

We also look for opportunities to expand our products into additional patient populations through clinical trials, new indications, and select investigator-initiated studies.

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 are now determining the next steps for this program.

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, including Sancuso, FDA products approved for sale in the United States.

Through our international partners, we are also working to bring our medicines to patients in their countries.

Additionally, we look for opportunities to expand our products into additional patient populations through clinical trials, new presentations and our support of select, investigator-initiated studies.

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 to address unmet medical needs.

Further, we are supplementing these activities with the early stage drug development activities at CET, our majority-owned subsidiary.

Specifically, we are seeking long term sustainable growth by executing the following plans:

Support and expand the use of our marketed products.

Our clinical team is developing a pipeline of new product candidates largely 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.

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

Supporting and expanding the use of our marketed products.

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

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As examples, we have secured pediatric approval, expanding the labeling for both our Acetadote and Caldolor brands.

Selectively add complementary brands.

Selectively adding complementary brands.

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.

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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 Vibativ represents the largest product acquisition we have completed.

Progress clinical pipeline and incubate future product opportunities at CET.

We believe it is important to build a pipeline of innovative new product opportunities.

Our ifetroban Phase II development programs represent the implementation of this strategy.

At CET, we are supplementing our acquisition and late-stage development activities with the early-stage drug development activities.

Our acquisition of Vibativ and Sancuso are examples of this strategy.

Progressing clinical pipeline and incubate future product opportunities at CET.

We believe it is important to build a pipeline of innovative new product opportunities, as we are doing though our ifetroban Phase II development programs.

We are also supplementing our acquisitions and late-stage development activities with early-stage drug development activities with CET.

CET partners with universities and other research organizations to develop promising, early-stage product candidates, which Cumberland has the opportunity to further develop and commercialize.

Leverage our infrastructure through co-promotion partnerships.

Leveraging our infrastructure through co-promotion partnerships.

We believe that our commercial infrastructure can help drive prescription volume and product sales.

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

Our co-promotion partnership with Poly Pharmaceuticals, Inc.

and Foxland Pharmaceuticals, Inc.

allow us to expand the support for Kristalose across the United States.

Build an international contribution to our business.

We have established our own commercial capabilities, including two sales divisions to cover the U.S.

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.

Building an international contribution to our business.

We have established our own commercial capabilities, including three sales divisions, to cover the U.S.

market for our products.

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

Manage our operations with financial discipline.

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.

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SALES AND MARKETING

Our sales and marketing team has broad industry experience in selling branded pharmaceuticals.

Our sales and marketing professionals manage our dedicated hospital and gastroenterology sales forces, including approximately 50 sales representatives and district managers, direct our national marketing campaigns and maintain key national account relationships.

Cumberland's sales and marketing team has broad industry experience in selling branded pharmaceuticals.

Our sales and marketing executives direct our national marketing campaigns and maintain key national account relationships.

They also manage our dedicated hospital, field and oncology sales forces – which are comprised of approximately 60 sales professionals.

Hospital market:

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We believe the hospital market is under-served and highly concentrated, and that it can be penetrated effectively by a small, dedicated sales force without large-scale promotional activity.

Our established position in the hospital market provided the rationale for adding Vibativ as our first infectious disease product that complement our hospital product line.

Our strategy has been to increase the focus of our hospital sales team on targeted, high priority accounts.

Our established position in the hospital market provided the rationale for adding Vibativ as our first infectious disease product that complements our hospital product line.

Our strategy has been to focus our hospital sales team on select, high priority accounts.

Gastroenterology and rheumatology market:

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Because the markets for gastrointestinal and rheumatology diseases are broad in patient scope, yet relatively narrow in physician base, we believe they provide opportunities that can be penetrated with a modest sized sales force.

By investing in our sales and marketing activities we believe that we can increase market share for these products.

We believe that we can increase market share for these products through our sales and marketing activities.

Oncology market:

In early 2022, we formed a new oncology sales force to promote our Sancuso brand.

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

This organization targets key oncologists and clinics across the U.S.

and is comprised of both insider and field based sales professionals.

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

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

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We also regularly attend select medical meetings and trade shows to expand the awareness of our products.

Our national accounts function is responsible for key large buyers and related marketing programs.

National accounts maintain relationships with our wholesaler customers as well as with third-party payors such as group purchasing organizations, pharmacy benefit managers, hospital buying groups, state and federal government purchasers and health insurance companies.

Our national accounts team is responsible for key large buyers and related marketing programs.

This team maintains relationships with our wholesaler customers as well as with third-party payors such as group purchasing organizations, pharmacy benefit managers, hospital buying groups, out-patient centers, state and federal government purchasers and health insurance companies.

MATERIAL CUSTOMERS

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Caldolor India, Pakistan, Bangladesh and Nepal Marketed

GerminMED Caldolor Qutar Marketed

GerminMED Caldolor Qatar Marketed

R-Pharm JSC Vibativ Russia Marketed

ETHICA Industri Farmasi Caldolor Indonesia Registration

Laboratorios Grifols, S.A.

Caldolor Spain, Portugal and South America Registration

SciClone Pharmaceuticals, Inc.

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• Manufacturing and providing finished product for sale.

During 2020, we worked to support our existing international partners and to identify new companies to represent our products in select additional territories.

During 2021, we worked to support our existing international partners, conclude unproductive arrangements and identify new companies to represent our products in select additional territories.

BUSINESS DEVELOPMENT

Since inception, we have had an active business development initiative focused on acquiring rights to marketed products and product candidates that fit our strategy and target markets.

We source business development opportunities through our international network of advisory firms and individual pharmaceutical industry and medical advisors.

A multi-disciplinary internal management team reviews these opportunities on a regular basis using a group of selection criteria.

We have historically focused on product opportunities that are a strategic fit with our commercial organization, development expertise and medical focus, employing a variety of transaction structures.

We have continued to build our product portfolio of complementary, niche brands largely through product acquisitions and late-stage development of product candidates.

Our primary targets are under-promoted, FDA - approved drugs with existing brand recognition and late-stage development product candidates that address unmet or poorly met medical needs in the hospital acute care and gastroenterology, rheumatology and oncology markets.

We believe that by focusing mainly on approved or late-stage products, we can minimize the significant risk, cost and time associated with drug development.

We continue to strategically review our brands, pipeline and capabilities, as well as our international partners.

We believe that it is prudent to continually evaluate our product portfolio, partners, and organization in order to ensure a proper focus and the needed supporting capabilities.

International Partners

Pharm Korea Co., Ltd.

Pharm”) has licensed our Caldolor product for the South Korean market, and they obtained regulatory approval for Caldolor in their country.

During 2021 D.B.

Pharm continued to purchase supplies of Caldolor and distributed the brand in South Korea.

We have also entered into agreements with D.B.

Pharm to register and commercialize our Vaprisol and Vibativ brands in their country.

During 2021 we worked with them to prepare the submissions for the approval of each brand there.

We have executed a License and Distribution agreement with HongKong WinHealth Pharma Group Co.

Limited (“WinHealth”) for our Caldolor and Acetadote brands in China and Hong Kong.

Under the terms of the agreement, WinHealth will provide development milestone payments and purchase supplies of the products following their registration in China.

We also entered into a Strategic Alliance agreement with WinHealth to explore future business opportunities that will further the mission and goals of each organization.

Founded in Hangzhou, China and currently headquartered in Hong Kong, WinHealth has developed a wide breadth of capabilities including drug licensing, product development and registration, and has established a strong network of distribution and sales promotional capabilities for the Chinese market.

WinHealth has established partnerships with international companies that include Boehringer-Ingelheim, Janssen, Novartis, Pfizer, and Roche, generating several hundred million dollars in sales annually.

In August 2020, we entered into an agreement with WinHealth Investment (Singapore) Ltd creating WHC Biopharmaceuticals, Pte.

The joint venture will focus on acquiring, developing, registering, and commercializing development stage and commercial stage biopharmaceuticals for China, Hong Kong and other Asian markets.

R-Pharma JSC (“R Pharma”) has licensed our Vibativ product for a territory that includes Russia and a number of adjacent countries in Eastern Europe.

R-Pharma is one of the leading multinational pharmaceutical organizations based in Russia.

Headquartered in Moscow and focusing in a wide breadth of therapeutic areas in the specialty and hospital care markets, R-Pharma generates $1 billion in annual revenue.

R-Pharma has registered Vibativ in Russia and during 2021 continued to purchase supplies of the product for that market.

In late 2021 we entered into a new agreement with R-Pharma for the terms associated with the supply of Vibativ for greater Russian territory.

SciClone Pharmaceuticals (Holdings) Limited (“SciClone”) has licensed our Vibativ product for sale and distribution in China and several adjacent countries.

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

SciClone expects a review period of up to twelve months for 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.

Poly Co-Promotion Agreement

We entered into a co-promotion arrangement with Poly Pharmaceuticals, Inc.

(“Poly”) for our Kristalose product in 2017.

Poly is a privately held U.S.

specialty pharmaceutical company that is featuring Kristalose to an expanded number of physicians.

Poly’s sales organization is more than doubling the number of nationwide physicians that are reached with the Kristalose brand message.

During 2019, we extended our co-promotion arrangement with Poly.

2R and Foxland Agreements

During 2018, we entered into another co-promotion arrangement related to our Kristalose product.

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

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

Nordic License Agreement

We acquired the exclusive U.S.

rights to Nordic Group B.V.'s injectable methotrexate product line.

The product line is approved for patient use in various European countries.

Cumberland has registered and is commercializing the methotrexate products under the brand name RediTrex.

The products are designed for the treatment of active rheumatoid arthritis, juvenile idiopathic arthritis, severe psoriatic arthritis, and severe disabling psoriasis.

Following the FDA approval for RediTrex, we began introducing the product line during 2020 and commenced the full national launch in October 2021.

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

Through CET, we collaborate with a select group of academic research institutions located in the mid-south region of the U.S.

to identify, co-develop and seek grant funding for promising biomedical technologies emerging from those research institutions.

CET has entered into a series of agreements to access and collaborate on the development of innovative product candidates.

These arrangements enable CET to team with university-based researchers to advance their scientific discoveries and breakthroughs by designing new product candidates to improve patient care and address unmet medical needs.

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.

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.

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.

Clinical Development

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• monitoring applicable third-party service providers for quality and compliance with current Good Manufacturing Practices ("GMPs"), Good Laboratory Practices ("GLPs"), and Good Clinical Practices ("GCPs"), and performing periodic audits of such vendors;

• maintaining systems for document control, product and process change control, customer complaint handling, product stability studies and annual drug product reviews.

• maintaining systems for document control, product and process change control, customer complaint.

PROFESSIONAL AND MEDICAL AFFAIRS

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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 November 2018, Cumberland reached an agreement to acquire Vibativ from Theravance Biopharma and assume global responsibility for the product.

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.

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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 7 years, from 2011 through 2017.

Caldolor Clinical Manuscripts

In July 2020, Cumberland 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.

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.

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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.

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 candidates in 1) patients with cardiomyopathy associated with Duchenne Muscular Dystrophy, a rare, fatal, genetic neuromuscular disease results in deterioration of the skeletal, heart and lung muscles, 2) Systemic Sclerosis or scleroderma, a debilitating autoimmune disorder characterized by diffuse fibrosis of the skin and internal organs and 3) Aspirin-Exacerbated Respiratory Disease, a severe form of asthma.

In addition, we have 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.

We have three Phase II clinical programs underway evaluating 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 rare, fatal, genetic neuromuscular disease results in deterioration of the skeletal, heart and lung muscles.

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 2020 due to the COVID-19 pandemic.

While enrollment of new patients is currently limited, we have worked to ensure that patients already entered into a trial continue to receive their study drug.

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

Many of our clinical study sites have reopened and resumed screening of patients for potential enrollment into our studies.

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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.

During 2017, we completed a Phase I study which defined the pharmacokinetic properties and provided a favorable safety profile for this new product candidate.

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.

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We have completed the study report, filed it with the FDA and are now determining the next steps for this product development program.

BUSINESS DEVELOPMENT

Since inception, we have had an active business development program focused on acquiring rights to marketed products and product candidates that fit our strategy and target markets.

We source business development opportunities through our international network of advisory firms and individual pharmaceutical industry and medical advisors.

A multi-disciplinary internal management team reviews these opportunities on a regular basis using a list of selection criteria.

We intend to continue to build a portfolio of complementary, niche products largely through product acquisitions and late-stage product development.

Our primary targets are under-promoted, FDA approved drugs with existing brand recognition and late-stage development product candidates that address unmet or poorly met medical needs in the hospital acute care and gastroenterology markets.

We believe that by focusing mainly on approved or late-stage products, we can minimize the significant risk, cost and time associated with drug development.

Early in 2019, we announced a strategic review of our brands, capabilities, and international partners.

This review followed an accelerated business development initiative, which resulted in a series of transactions.

Because of that progress, we felt that it was prudent to take a fresh look at our product portfolio, partners, and organization to ensure proper focus and capabilities.

International Partners

As a result of our strategic review, we altered our international arrangements through several new agreements as well as dissolution of prior agreements..

We executed a License and Distribution agreement with HongKong WinHealth Pharma Group Co.

Limited (“WinHealth”) for our Caldolor and Acetadote brands in China and Hong Kong.

Under the terms of the agreement, WinHealth will provide development milestone payments and purchase supplies of the products following their registration in China.

We also entered into a Strategic Alliance agreement with WinHealth to explore future business opportunities that will further the mission and goals of each organization.

WinHealth has established partnerships with international companies that include Boehringer-Ingelheim, Janssen, Novartis, Pfizer, and Roche, generating approximately $330 million in annual sales in 2018.

In August 2020, we entered into an agreement with WinHealth Investment (Singapore) Ltd creating WHC Biopharmaceuticals, Pte.

The joint venture will focus on acquiring, developing, registering, and commercializing development stage and commercial stage biopharmaceuticals for China, Hong Kong and other Asian markets.

Additionally, we completed the assignment and amendment of a Commercialization Agreement with R-Pharma JSC (“R Pharma”) associated with ongoing distribution of Vibativ in Russia and a number of adjacent countries in Eastern Europe.

R-Pharma is one of the leading multinational pharmaceutical organizations based in Russia.

Headquartered in Moscow and focusing in a wide breadth of therapeutic areas in the specialty and hospital care markets, R-Pharma generated over $1.6 billion in revenues in 2018.

We are in the process of concluding our Commercialization Agreement with Hikma Pharmaceuticals LLC to register and distribute Vibativ in a number of countries throughout the Middle East, our agreement with Dr.

Reddy’s Laboratories Limited for the registration and distribution of Vibativ in India, and our License and Distribution Agreement with PT.

EHTICA Industri Farmasi for the registration and distribution of Caldolor in Indonesia.

Poly Co-Promotion Agreement

We entered into a co-promotion arrangement with Poly Pharmaceuticals, Inc.

(“Poly”) for our Kristalose product in 2017.

Poly is a privately held U.S.

specialty pharmaceutical company that is featuring Kristalose to an expanded number of physicians.

Poly’s sales organization is more than doubling the number of nationwide physicians that are reached with the Kristalose brand message.

During 2019, we extended our co-promotion arrangement with Poly.

Nordic License Agreement

In November 2016, we announced our agreement to acquire the exclusive U.S.

rights to Nordic Group B.V.'s injectable methotrexate product line.

The products are designed for the treatment of active rheumatoid arthritis, juvenile idiopathic arthritis, severe psoriatic arthritis, and severe disabling psoriasis.

The product line is approved for patient use in various European countries and received FDA approval near the end of 2019.

Cumberland has registered and is commercializing the methotrexate products in the United States under the brand name RediTrex.

2R and Foxland Agreements

During 2018, we entered into another co-promotion arrangement related to our Kristalose product.

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

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

Cumberland continues to manage the regulatory activities associated with the product.

Clinigen Strategic Dissolution Agreement

We previously entered into a strategic alliance 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 will return 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 will no longer be 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 will receive $5 million in financial consideration paid over the two-years following December 31, 2019.

CET University Collaboration Agreements

Through CET, we collaborate with a select group of academic research institutions located in the mid-south region of the U.S.

to identify, co-develop and seek grant funding for promising biomedical technologies emerging from those research institutions .

CET is collaborating with Vanderbilt University, the University of Mississippi, the University of Tennessee Research Foundation, Louisiana State University, and the Medical University of South Carolina to identify, co-develop and seek grant funding for promising biomedical technologies emerging from those research institutions.

MANUFACTURING AND DISTRIBUTION

Manufacturing

We partner with third parties for certain non-core, capital-intensive capabilities, including the manufacturing and distribution of our products.

We manage these third-party relationships and are responsible for the quality review and release of each lot of our products.

For Acetadote we had agreements with two manufacturers, and one manufacturer provided commercial supplies of the product during 2020.

We have agreements with multiple manufacturers for the supply of Caldolor and during 2020 we obtained commercial supplies from three of these manufacturers for our international and domestic Caldolor requirements.

We have an agreement for the purchase of Kristalose API with an international supplier.

We also have manufacturing relationships with two packagers who provided finished supplies of the product for commercial and sampling purposes during 2020.

Omeclamox-Pak ®

Prior to our asset purchase agreement with GEL that closed in December 2018, GEL managed the packaging and supply of Omeclamox-Pak commercial and sample units.

Following our acquisition of the remaining rights to the brand in late 2018, we assumed responsibility for the packaging and supply of the product.

During 2019 we entered into a new packaging arrangement for this product.

During 2020, the packager for Cumberland’s Omeclamox-Pak product encountered financial difficulties due to the economic impact of COVID-19, and their operations suspended.

Cumberland is awaiting resumption of those operations while also exploring other alternatives to restart the product’s packaging.

We informed the FDA of a shortage of the Omeclamox-Pak effective October 14, 2020, and have not provided a date for the availability of new inventory.

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

In addition, as part of that transaction, we were assigned a commercial supply agreement with the historical Vaprisol manufacturer.

In 2018, the manufacturer informed us that they would no longer be able to provide the product following the manufacturing of one final batch which is providing us with a multi-year supply.

We identified and reached an agreement during 2020 with a new manufacturer to provide us with long term supplies of the product.

We subsequently initiated the transfer of the product’s manufacturing to the new facility in 2020.

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

As a result of the agreement, we are now responsible for the future manufacture of the product and completed the transfer of the product’s manufacturing activities to a new supplier and received FDA approval for that facility in 2020.

In 2016, we entered into an agreement with the Nordic Group B.V.

("Nordic") to acquire the exclusive U.S.

rights to Nordic’s injectable methotrexate product line.

In 2019, we received FDA approval for the product and authorization to market them under the RediTrex brand name.

Under our agreement with Nordic, they are responsible for providing us the packaged and labeled commercial supply of RediTrex.

Like many pharmaceutical companies, we engage a third-party with appropriate facilities and logistical expertise to support the U.S.

distribution of our products.

Cardinal Health has exclusively handled our U.S.

product logistics activities, including warehousing, shipping, and various other customer activities.

Our primary customers are the wholesalers of pharmaceuticals who provide our products to hospitals, clinics and retail pharmacies in the U.S.

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.

CORPORATE DEVELOPMENT

Cumberland Foundation

In December 2017, we formed the Cumberland Pharma Foundation (the "Foundation") to serve as a vehicle to facilitate the ongoing philanthropic endeavors of Cumberland Pharmaceuticals Inc.

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

The Foundation was formed as an independent, nonprofit corporation designed to qualify as a tax-exempt organization pursuant to Section 501(a) of the Internal Revenue Code.

The Foundation’s Board of Directors is comprised of Cumberland Pharmaceuticals executives who are responsible for overseeing the Foundation’s ongoing activities including charitable contributions.

During 2018, we provided a grant of 50,000 shares of our common stock to the Foundation.

We initially provided a grant of 50,000 shares of our common stock to the Foundation.

The shares will address the ongoing financial needs of the Foundation, with most of the shares expected to be held for the opportunity to realize long term appreciation to support the Foundation’s future.

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Cumberland Health and Wellness Political Action Committee

In November 2017 we formed the Cumberland Health and Wellness Political Action Committee (PAC).

We have also formed the Cumberland Health and Wellness Political Action Committee (the “PAC”).

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

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The PAC received initial funding from us, and future funding will include voluntary individual contributions from Cumberland Pharmaceuticals directors and employees.

MANUFACTURING AND DISTRIBUTION

Manufacturing

We partner with third parties for certain non-core, capital-intensive capabilities, including the manufacturing and distribution of our products.

We manage these third-party relationships and are responsible for the quality review and release of each lot of our products.

We have an agreement with one manufacturer, who provided commercial supplies of Acetadote in 2021.

We have agreements with multiple manufacturers for the supply of Caldolor and during 2021 we obtained commercial supplies from three of these manufacturers for our international and domestic Caldolor requirements.

We have an agreement for the purchase of Kristalose API with an international supplier.

We also had manufacturing relationships with two packagers who provided finished supplies of the product for commercial and sampling purposes during 2021.

We will continue with one of those facilities in 2022.

Omeclamox-Pak ®

During 2020, the packager for Cumberland’s Omeclamox-Pak product encountered financial difficulties due to the economic impact of COVID-19, and their operations suspended.

Cumberland is awaiting resumption of those operations while also exploring other alternatives to restart the product’s packaging.

We informed the FDA of a shortage of the Omeclamox-Pak in October 2020, and have not provided a date for the availability of new inventory.

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.

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 are additional lots planned for 2022 which will provide us with additional supplies.

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

Data is being developed to support the transfer which will require FDA approval.

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

We reached an agreement during 2020 with a new manufacturer to provide us with long - term supplies of the product.

We subsequently completed the transfer of the product’s manufacturing to the new facility in 2021.

We informed the FDA that supplies of the product are not currently available and are awaiting approval for that new facility.

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

Like many pharmaceutical companies, we engage a third-party with appropriate facilities and logistical expertise to support the U.S.

distribution of our products.

In 2021, Cardinal Health Specialty Solutions has exclusively handled our U.S.

product logistics activities, including warehousing, shipping, and various other customer activities.

Our primary customers are the wholesalers of pharmaceuticals who provide our products to hospitals, clinics and retail pharmacies in the U.S.

PATENTS, TRADEMARKS AND OTHER INTELLECTUAL PROPRIETARY RIGHTS

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The claims of the 356 Acetadote Patent encompass the new Acetadote formulation and include composition of matter claims.

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

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.

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Patent number 8,653,061 (the “061 Acetadote Patent”) which is assigned to us.

The claims of the 061 Acetadote Patent encompass the use of the 200 mg/ml Acetadote formulation

to treat patients with acetaminophen overdose.

The claims of the 061 Acetadote Patent encompass the use of the 200 mg/ml Acetadote formulation to treat patients with acetaminophen overdose.

Following its issuance, the 061 Acetadote Patent was listed in the FDA Orange Book.

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On November 3, 2017, we became aware of a Paragraph IV certification notice from Exela Pharma Sciences, LLC challenging the 356, 445, 061, 738, and 028 Acetadote Patents on the basis of non-infringement.

We are considering our legal options and intend to continue to vigorously defend and protect our Acetadote product and related intellectual property rights.

We are the owner of U.S.

6,727,286, which encompasses ibuprofen solution formulations, methods of making the same, and methods of using the same, and which is scheduled to expire in November 2021.

patent is listed in the FDA Orange Book and is associated with our completed international application No.

PCT/US01/42894.

We have filed for international patent protection in association with this PCT application in various countries, several of which have been allowed.

We have an exclusive, worldwide license to clinical data for intravenous ibuprofen from Vanderbilt University, in consideration for royalty obligations related to Caldolor.

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We own numerous U.S.

patents and related international patents for Vaprisol.

These patents were acquired in our February 2014 acquisition of certain product rights, intellectual property and related assets of Vaprisol from Astellas.

We own numerous U.S.

patents and related international patents for Vibativ.

These patents were acquired in our November 2018 acquisition of certain product rights, intellectual property and related assets of Vibativ from Theravance.

Eleven Vibativ patents are listed in the FDA Orange Book.

Three Vibativ patents are listed in the FDA Orange Book.

Patent number 7,531,623 (the “623 Vibativ Patent”) is scheduled to expire in January 2027 and includes composition of matter claims that encompass the Vibativ drug substance as well as methods for preparing the Vibativ drug substance.

We are the owner of U.S.

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.

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

The 282 Sancuso Patent includes composition of matter claims that encompass the Sancuso drug product as well as methods of using Sancuso for treatment and/or prophylaxis.

Remaining Products

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

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

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

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We believe non-narcotic analgesics for the treatment of post-surgical pain are the primary potential competitors to Caldolor.

In addition to the injectable analgesic products above, many companies are developing analgesics for specific indications such as migraine and neuropathic pain, oral extended-release forms of existing narcotic and non-narcotic products, and products with new methods of delivery such as transdermal.

In addition to the injectable analgesic products above, many companies are developing analgesics for specific indications such as migraine and neuropathic pain, oral extended-release forms of existing narcotic and non-narcotic products, as well as those with new methods of delivery such as transdermal.

We are not aware of any approved injectable products indicated for the treatment of fever in the U.S.

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MiraLax (polyethylene glycol 3350), previously a prescription product, was indicated for the treatment of constipation and manufactured and marketed by Bayer.

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.

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

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• 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.

Recommended treatment suggests the patch be applied 24 to 48 hours prior to chemotherapy treatment and remain in place for 5 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.

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

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

Effective November 12, 2018, Cumberland acquired the worldwide rights to Vibativ (telavancin) from Theravance Biopharma.

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

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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.

RediTrex was introduced by Cumberland in the fourth quarter of 2020.