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TUESDAY, Sept. 4, 2024 -- An overgrowth of gut microorganisms that produce methane could be a cause of severe constipation in many people, a new review finds. These gut bugs belong to a class of microbe called archaea, and when they flourish too well in a person’s gut they cause a condition called intestinal methanogen overgrowth (IMO), researchers explained. People with IMO are twice as likely to have constipation as those with a healthy gut, researchers found. “Our study found that patients with IMO are more likely to have constipation, particularly severe constipation, and less likely to have unyielding diarrhea,” said senior researcher Dr. Ali Rezaie , medical director of the Cedars-Sinai GI Motility Program. The human gut is colonized with trillions of microscopic organisms, including bacteria, viruses, fungi and archaea. These organisms typically help humans by performing services important to health, such as helping digest food and manage immune reactions. However, harmful microbes can crowd out the helpful ones and create health problems. One example is C. difficile , a bacteria that can cause terrible diarrhea if it colonizes the gut. For this review, researchers looked at archaea, a type of microorganism distinct from either bacteria or fungi, and how they might cause GI problems. Constipation is one of the most common gut problems in the United States, researchers said in background notes. About 16% of adults have constipation and the numbers nearly double for people over 60. Constipation typically has been chalked up to causes like a lack of fiber or medication side effects, but researchers suspected that gut microbe makeup might also play a role in the condition. The research team pooled data from 19 studies that assessed symptoms of patients with IMO, including 11 conducted in the United States and eight in other countries. All together, the studies included nearly 1,300 people with IMO and compared them to more than 3,200 healthy controls. IMO can be detected through a simple breath test, Rezaie said. “When there is an excessive amount of archaea in your gut, they produce more methane, and some of that methane makes its way to your bloodstream, then to your lungs, and you breathe it out, where it can measured as a diagnostic test,” Rezaie explained in a Cedars Sinai release. “Essentially, people who have excessive amounts of methane have a lot of GI symptoms, including constipation, flatulence, bloating and diarrhea.” About 47% of people with IMO suffered from severe constipation, compared with 38% of controls, the pooled data revealed. They also were more likely to suffer severe constipation. On the other hand, they were less likely than controls to suffer from diarrhea, 37% versus 52%. The review was published recently in the journal Clinical Gastroenterology and Hepatology . The cure for IMO-induced constipation likely involves a combination of antibiotics and a specialized diet intended to boost healthy gut microbes, researchers said. The most commonly used treatment, laxatives, can temporarily relieve constipation but won’t address the root cause of the problem. However, it’s important to first diagnose archaea overgrowth by giving patients a breath test, researchers said. “The goal is to move toward developing specific therapies and personalized treatment for a subgroup of people who experience constipation due to IMO,” Rezaie said. “We can start by using breath tests to identify excessive methane production, which can be the first step to detecting archaea overgrowth and could ultimately lead to developing more targeted therapies,” Rezaie added. “It's a big step to move away from the common reflex use of laxatives.” Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

TRV045, novel S1P receptor modulator in development for the treatment of acute and chronic neuropathic pain and epilepsy, demonstrated sustained long-term analgesic effect and differentiated mechanism of action in preclinical models $12 million financing completed, including non-dilutive $2 million tranche and $10 million reduction in liabilities associated with existing ex-US royalty financing CHESTERBROOK, Pa., Aug. 08, 2024 (GLOBE NEWSWIRE) -- Trevena, Inc. (Nasdaq: TRVN), a biopharmaceutical company focused on the development and commercialization of novel medicines for patients with central nervous system (CNS) disorders, today reported its financial results for the second quarter ended June 30, 2024 and provided an overview of its recent operational highlights. “We have continued to advance TRV045 in the second quarter,” said Carrie Bourdow, President and CEO of Trevena. “We believe the most recent data further supports TRV045’s therapeutic potential and differentiated MOA and its potential to address the need for novel, non-opioid therapies for treating neuropathic pain and epilepsy.” Second Quarter 2024 and Recent Corporate Highlights TRV045 preclinical data further supports its therapeutic potential and differentiated mechanism of action. TRV045 showed potential for sustained, long-term analgesic effect in a preclinical model of neuropathic pain, with no evidence of receptor desensitization. TRV045 also demonstrated a statistically significant, dose-dependent increase in measures of seizure threshold and showed seizure protection in validated preclinical models. $12 million financing completed, including receipt of non-dilutive $2 million tranche, $10 million reduction in outstanding liabilities, and potential $8 million in OLINVYK US partnering and commercial milestones. In the previously announced amendment to its March 2022 ex-US royalty-based financing with R-Bridge Healthcare Fund, Trevena received a $2 million payment from R-Bridge and is eligible to receive $8 million in future tranches based on the achievement of certain US partnering and commercial milestones for OLINVYK. In addition, the outstanding liability in connection with the Royalty Financing was reduced by $10 million in connection with the Amendment. Trevena previously received $30 million in non-dilutive funding under the Royalty Financing.OLINVYK strategic review. The Company continues its review of strategic alternatives for OLINVYK. There can be no assurance regarding the schedule for completion of the strategic review process, that this strategic review process will result in the Company pursuing any transaction or that any transaction, if pursued, will be completed. Potential strategic alternatives that may be explored or evaluated include, but are not limited to, a sale, license, divestiture or discontinuation of US commercial sales of OLINVYK. Financial Results and Other Updates for First Quarter 2024For the second quarter of 2024, the Company reported a net loss attributable to common stockholders of $4.9 million, or $0.23 per share, compared to $8.0 million, or $0.69 per share in the second quarter of 2023. Cash and cash equivalents were $16.4 million as of June 30, 2024, not including the $2 million in gross proceeds received from R-Bridge in July 2024. About Trevena Trevena, Inc. is a biopharmaceutical company focused on the development and commercialization of innovative medicines for patients with CNS disorders. The Company has one approved product in the United States, OLINVYK® (oliceridine) injection, indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. The Company’s novel pipeline is based on Nobel Prize winning research and includes three differentiated investigational drug candidates: TRV045 for diabetic neuropathic pain and epilepsy, TRV250 for the acute treatment of migraine and TRV734 for maintenance treatment of opioid use disorder. For more information, please visit www.Trevena.com About TRV045 TRV045 is a novel, highly selective sphingosine-1-phosphate subtype 1 (S1P1) receptor modulator being developed as a potential treatment for acute and chronic neuropathic pain secondary to diabetic peripheral neuropathy. Through a collaboration with the National Institutes of Health, Trevena is also exploring TRV045 as a potential treatment for epilepsy. S1P receptors are located throughout the body, including the central nervous system, where they are believed to play a role in modulating neurotransmission and membrane excitability. Trevena’s discovery efforts have identified a family of compounds that are highly selective for the S1P1 receptor. TRV045 reversed thermal hyperalgesia, a measure of neuropathic pain, in nonclinical models of diabetic peripheral neuropathy and chemotherapy-induced peripheral neuropathy. TRV045 was not associated with lymphopenia and produced no changes in blood pressure, heart rate, or respiratory function at or above pharmacologically active doses in nonclinical studies. TRV045 is an investigational product and is not yet approved by the FDA. Subjects in both studies referenced in this press release were enrolled outside of the United States, and the studies were not conducted under the Investigational New Drug Application for TRV045. About OLINVYK® (oliceridine) injection OLINVYK is a new chemical entity approved by the FDA in August 2020. OLINVYK contains oliceridine, an opioid, which is a Schedule II controlled substance with a high potential for abuse similar to other opioids. It is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. OLINVYK is available in 1 mg/1 mL and 2 mg/2 mL single-dose vials, and a 30 mg/30 mL single-patient-use vial for patient-controlled analgesia (PCA). Approved PCA doses are 0.35 mg and 0.5 mg and doses greater than 3 mg should not be administered. The cumulative daily dose should not exceed 27 mg. Please see Important Safety Information, including the BOXED WARNING, and full prescribing information at www.OLINVYK.com. IMPORTANT SAFETY INFORMATION WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF OLINVYK Addiction, Abuse, and Misuse Because the use of OLINVYK exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of OLINVYK, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of OLINVYK are essential. Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of OLINVYK and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Neonatal Opioid Withdrawal Syndrome If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of NOWS, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery. INDICATIONS AND USAGE OLINVYK is an opioid agonist indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, reserve OLINVYK for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: Have not been tolerated or are not expected to be tolerated.Have not provided adequate analgesia or are not expected to provide adequate analgesia. The cumulative total daily dose should not exceed 27 mg. CONTRAINDICATIONS OLINVYK is contraindicated in patients with: Significant respiratory depressionAcute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipmentKnown or suspected gastrointestinal obstruction, including paralytic ileusKnown hypersensitivity to oliceridine (e.g. anaphylaxis) WARNINGS AND PRECAUTIONS OLINVYK contains oliceridine, a Schedule II controlled substance, that exposes users to the risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed OLINVYK. Assess risk, counsel, and monitor all patients receiving opioids.Serious, life-threatening respiratory depression has been reported with the use of opioids, even when used as recommended, especially in patients with chronic pulmonary disease, or in elderly, cachectic and debilitated patients. The risk is greatest during initiation of OLINVYK therapy, following a dose increase, or when used with other drugs that depress respiration. Proper dosing of OLINVYK is essential, especially when converting patients from another opioid product to avoid overdose. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status.Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia with risk increasing in a dose-dependent fashion. In patients who present with CSA, consider decreasing the dose of opioid using best practices for opioid taper.Profound sedation, respiratory depression, coma, and death may result from the concomitant use of OLINVYK with benzodiazepines and/or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, or alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate, prescribe the lowest effective dose, and minimize the duration.Use of OLINVYK for an extended period of time during pregnancy can result in withdrawal in the neonate that may be life-threatening. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.OLINVYK was shown to have mild QTc interval prolongation in thorough QT studies where patients were dosed up to 27 mg. Total cumulative daily doses exceeding 27 mg per day were not studied and may increase the risk for QTc interval prolongation. Therefore, the cumulative total daily dose of OLINVYK should not exceed 27 mg.Increased plasma concentrations of OLINVYK may occur in patients with decreased Cytochrome P450 (CYP) 2D6 function or normal metabolizers taking moderate or strong CYP2D6 inhibitors; also in patients taking a moderate or strong CYP3A4 inhibitor, in patients with decreased CYP2D6 function who are also receiving a moderate or strong CYP3A4 inhibitor, or with discontinuation of a CYP3A4 inducer. These patients may require less frequent dosing and should be closely monitored for respiratory depression and sedation at frequent intervals. Concomitant use of OLINVYK with CYP3A4 inducers or discontinuation of a moderate or strong CYP3A4 inhibitor can lower the expected concentration, which may decrease efficacy, and may require supplemental doses.Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. This differs from tolerance where increasing doses are required to maintain the desired effect. Symptoms of OIH include, but may not be limited to, increased levels of pain upon dose increase, decreased levels of pain upon dose decrease, or pain from ordinarily non-painful stimuli (allodynia). These symptoms may suggest OIH only if there is no evidence of disease progression, opioid tolerance, withdrawal, or addictive behavior. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation.Cases of adrenal insufficiency have been reported with opioid use (usually greater than one month). Presentation and symptoms may be nonspecific and include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If confirmed, treat with physiologic replacement doses of corticosteroids and wean patient from the opioid.OLINVYK may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor these patients for signs of hypotension. In patients with circulatory shock, avoid the use of OLINVYK as it may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of OLINVYK in patients with impaired consciousness or coma. OLINVYK should be used with caution in patients who may be susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased intracranial pressure or brain tumors, as a reduction in respiratory drive and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy.As with all opioids, OLINVYK may cause spasm of the sphincter of Oddi, and may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.OLINVYK may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures in vulnerable patients. Monitor patients with a history of seizure disorders for worsened seizure control.Do not abruptly discontinue OLINVYK in a patient physically dependent on opioids. Gradually taper the dosage to avoid a withdrawal syndrome and return of pain. Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving OLINVYK, as they may reduce the analgesic effect and/or precipitate withdrawal symptoms.OLINVYK may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.Although self-administration of opioids by patient-controlled analgesia (PCA) may allow each patient to individually titrate to an acceptable level of analgesia, PCA administration has resulted in adverse outcomes and episodes of respiratory depression. Health care providers and family members monitoring patients receiving PCA analgesia should be instructed in the need for appropriate monitoring for excessive sedation, respiratory depression, or other adverse effects of opioid medications. ADVERSE REACTIONS Adverse reactions are described in greater detail in the Prescribing Information. The most common (incidence ≥10%) adverse reactions in Phase 3 controlled clinical trials were nausea, vomiting, dizziness, headache, constipation, pruritus, and hypoxia. MEDICAL INFORMATION For medical inquiries or to report an adverse event, other safety-related information or product complaints for a company product, please contact the Trevena Medical Information Contact Center at 1-844-465-4686 or email MedInfo@Trevena.com. You are encouraged to report suspected adverse events of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. PLEASE see www.OLINVYK.com for full prescribing information including BOXED warning and important safety information Forward-Looking Statements Any statements in this press release about future expectations, plans and prospects for the Company, including statements about the Company’s strategy, future operations, clinical development and trials of its therapeutic candidates, plans for potential future product candidates and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “suggest,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the expectations surrounding the continued advancement of the Company’s product pipeline; the potential safety and efficacy of the Company’s product candidates and their regulatory and clinical development; the Company’s intention to pursue strategic alternatives for OLINVYK and the ability of any such strategic alternative to provide shareholder value; the expected financial and operational impacts of the Company’s decision to reduce commercial support for OLINVYK; the status, timing, costs, results and interpretation of the Company’s clinical trials or any future trials of any of the Company’s investigational drug candidates; the uncertainties inherent in conducting clinical trials; expectations for regulatory interactions, submissions and approvals, including the Company’s assessment of discussions with FDA; available funding; uncertainties related to continued listing on NASDAQ; uncertainties related to the Company’s intellectual property; uncertainties related to other matters that could affect the availability or commercial potential of the Company’s therapeutic candidates and approved product; and other factors discussed in the Risk Factors set forth in the Company’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings the Company makes with the SEC from time to time. In addition, the forward-looking statements included in this press release represent the Company’s views only as of the date hereof. The Company anticipates that subsequent events and developments may cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, except as may be required by law. For more information, please contact: Company Contact: Bob YoderSVP, Chief Business Officer & Head of Commercial OperationsTrevena, Inc.(610) 354-8840 TREVENA, INC.Condensed Statements of Operations (Unaudited, in thousands except share and per share data) Three Months Ended Jun 30, Six Months Ended Jun 30, 2024 2023 2024 2023 Product revenue $14 $21 $34 $27 License revenue 311 3,000 311 3,000 Total revenue 325 3,021 345 3,027 Operating expenses: Cost of goods sold 103 88 191 214 Selling, general and administrative 3,598 5,138 9,443 11,227 Research and development 3,127 3,991 7,092 7,900 Total operating expenses 6,828 9,217 16,726 19,341 Loss from operations (6,503) (6,196) (16,381) (16,314)Other income (expense) 1,612 (1,816) 3,812 483 Net loss $(4,891) $(8,012) $(12,569) $(15,831) Per share information: Net loss per share of common stock, basic and diluted ($0.23) ($0.69) ($0.59) ($1.49)Weighted average shares outstanding, basic and diluted 21,318,073 11,580,128 21,310,772 10,592,586 TREVENA, INC.Condensed Balance Sheets(Unaudited, in thousands) June 30, 2024 December 31, 2023Assets Current assets: Cash and cash equivalents $16,367 $32,975 Prepaid expenses and other current assets 1,664 2,230 Total current assets 18,031 35,205 Restricted cash 540 540 Property and equipment, net 1,018 1,195 Right-of-use lease assets 3,354 3,665 Total assets $22,943 $40,605 Liabilities and stockholders’ (deficit) equity Current liabilities: Accounts payable, net $1,132 $2,303 Accrued expenses and other current liabilities 3,002 4,239 Current portion of lease liabilities 1,072 1,012 Total current liabilities 5,206 7,554 Loans payable, net 31,527 30,809 Leases, net of current portion 3,875 4,424 Warrant liability 1,292 5,475 Total liabilities 41,900 48,262 Common stock 21 17 Additional paid-in capital 581,652 580,387 Accumulated deficit (600,630) (588,061)Total stockholders’ (deficit) equity (18,957) (7,657)Total liabilities and stockholders’ (deficit) equity $22,943 $40,605

NASHVILLE, Tenn., Aug. 6, 2024 /PRNewswire/ -- Cumberland Pharmaceuticals Inc. (Nasdaq: CPIX), a specialty pharmaceutical company, today announced significantly improved financial results and a favorable overall company performance for the second quarter of 2024. Highlights include: $9.9 million in net revenue during the second quarter of 2024, an increase of 16% sequentially from the first quarter of 2024. Adjusted earnings of $0.2 million, which represents a $0.8 million improvement over the prior period in 2024. $78.5 million in assets, $52.5 million in liabilities and $26.3 million of shareholders' equity. "We are very optimistic about our company's future, and we look forward to building on our second quarter success throughout the remainder of the year," said Cumberland's CEO, A.J. Kazimi. "Given the number of ongoing positive developments, we believe we're still on track to post significant revenue growth and positive cashflow from operations during 2024." RECENT DEVELOPMENTS INCLUDE: Kristalose ® Medicaid Coverage & Gastroenterology Guidelines Recommendation Wisconsin has added Kristalose, Cumberland's prescription-strength laxative, to its Medicaid formulary, and Cumberland is implementing a special initiative to announce this development in that market. Cumberland also has Medicaid coverage for the brand in New York state and Texas, two of the largest states for the product. Additionally, the American Gastroenterological Association's ("AGA") guidelines include Kristalose as a first-line treatment option for opioid-induced constipation. As the guidelines state, "Constipation is by far the most common and debilitating gastrointestinal effect of opioids, and some degree of constipation is near universal in patients taking opioid medications." Cumberland believes the AGA's recommendation will support the use of Kristalose in those patients. New Study Supports Vibativ ® as an Effective Treatment for Anthrax Infections In June, Antimicrobial Agents and Chemotherapy published a study evaluating Vibativ (telavancin) as a novel therapeutic against anthrax inhalation, the most dangerous form of those infections. Researchers were particularly interested in finding alternatives to current antibiotics in case anthrax bacteria become resistant to them. Researchers tested telavancin against 17 different anthrax strains in the lab to determine how well it could stop their growth. Additionally, researchers tested telavancin in rabbits that were infected with a deadly dose of airborne anthrax spores and compared telavancin's effectiveness to another antibiotic (levofloxacin) and a placebo. The results showed that: Telavancin was very effective at killing all the anthrax strains tested in the lab. In the preclinical study, all the animals treated with telavancin survived. Telavancin was better at clearing anthrax from the blood and organs than levofloxacin. Based on these results, the researchers concluded that telavancin could potentially be an effective new treatment option for anthrax infections, especially if current antibiotics become less effective due to resistance. Antimicrobial resistance continues to pose a significant challenge in the treatment of bacterial infections, necessitating the development of new antibiotic therapies. 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. Product Pipeline Cumberland has been evaluating its ifetroban product candidate, a selective thromboxane-prostanoid receptor antagonist, in a series of clinical studies. It has now been dosed in nearly 1,400 subjects and has been found to be safe and well tolerated in healthy volunteers and various patient populations. Cumberland has three Phase II clinical programs underway evaluating ifetroban in patients with 1) Systemic Sclerosis or scleroderma, a debilitating autoimmune disorder characterized by diffuse fibrosis of the skin and internal organs, 2) cardiomyopathy associated with Duchenne Muscular Dystrophy, a rare, fatal, genetic neuromuscular disease results in deterioration of the skeletal, heart, and lung muscles and 3) Idiopathic Pulmonary Fibrosis, the most common form of progressive fibrosing interstitial lung disease. This third program is our newest, with enrollment now underway. Cumberland recently applied for two U.S. Food and Drug Administration ("FDA") designations for its Duchenne Muscular Dystrophy product candidate: 1) Orphan Drug Designation, which is granted to products that show promise in the treatment, prevention or diagnosis of rare – or orphan – diseases; such designation can result in a number of benefits associated with the FDA review process including exclusivity after approval of the product. 2) Rare Pediatric Disease Designation, which is given to products intended to prevent or treat serious or life-threatening diseases that primarily affect children from birth to 18 years of age. Upon FDA approval this designation may result in a priority review voucher from the FDA for a different product. Cumberland expects to hear back from the FDA on both applications this year. Cumberland's plan going forward is to complete each of its company-sponsored studies, analyze their final data, announce top-line results and decide on the best development path for the registration of ifetroban, which Cumberland continues to believe has the potential to benefit many patients with orphan diseases that represent unmet medical needs. New Manufacturing & Supplies of Sancuso ® After acquiring U.S. rights to Sancuso, Cumberland successfully completed the transition from Kyowa Kirin to Cumberland in 2023, including the NDA transfer. A new manufacturing facility was approved by the FDA for Sancuso, and Cumberland has completed the first lots of Cumberland-packaged product there. Cumberland began shipping these new supplies of its Cumberland-branded product this summer. Federal NOPAIN Act Cumberland announced in April 2023 that it expected that Caldolor would be eligible for special Medicare reimbursement under the Non-Opioids Prevent Addiction in the Nation Act, which was enacted as part of the Consolidated Appropriations Act of 2023 (the "NOPAIN Act"). The NOPAIN Act requires Medicare to provide separate reimbursement for non-opioid products that are used to manage pain during surgeries conducted in hospital outpatient departments or in ambulatory surgical centers. The NOPAIN Act applies, in part, to products that are indicated to provide analgesia, without acting upon the body's opioid receptors. As a result, the Company expected that the NOPAIN Act would affect Medicare reimbursement for Caldolor, its non-opioid analgesic injection product. The reimbursement for non-opioid pain alternatives under the NOPAIN Act will apply to those products that are furnished between January 1, 2025 and January 1, 2028. It is anticipated that in late 2024, the Centers for Medicare & Medicaid Services ("CMS") will issue regulations implementing the NOPAIN Act and detailing the conditions for, and amount of, the separate reimbursement. In July 2023, in the Medicare Hospital Outpatient Prospective Payment System ("OPPS") Proposed Rule, CMS requested that manufacturers with potentially applicable non-opioid products submit comments and supporting clinical evidence regarding products that they believe should be eligible for separate payment. Cumberland submitted a comment letter along with the requisite clinical information to CMS in September 2023, explaining why Caldolor should be included and separately reimbursed. In July the 2024 Medicare OPPS Proposed Rule, CMS proposed that, in 2025, several drugs that were previously eligible for separate payment via existing CMS policies continue to be eligible for separate payment in the hospital outpatient setting under the Consolidated Appropriation Act 2023 and solicited comments on whether there are additional drugs or biologicals that meet the statutory definition. In response, Cumberland plans to submit a comment letter along with the requisite information in September 2024 and will then await information from CMS regarding the reimbursement status and price for Caldolor in the CY 2025 OPPS Final Rule. FINANCIAL RESULTS Net Revenue: For the three months ended June 30, 2024, net revenues were $9.9 million, a 16% increase from the first quarter of the year. Net revenue by product for the second quarter of 2024 included $4.1 million for Kristalose®, $2.5 million for Vibativ® $2.2 million for Sancuso® and $0.8 million for Caldolor®. Year-to-date 2024 net revenues were $18.3 million. Year-to-date net revenues by product were $7.3 million for Kristalose, $4.1 million for Vibativ, $4.0 million for Sancuso and $2.3 million for Caldolor. Operating Expenses: Total operating expenses were $10.9 million for the second quarter of 2024 and $21.2 million for the first half of the year. Net Income (Loss): The net loss for the second quarter of 2024 was $1.1 million, or $0.08 a share and a net loss of $3.0 million year to date, or $0.21 a share. Adjusted Earnings: Adjusted earnings for the second quarter of 2024 were $0.2 million, or $0.01 per share which is a $0.8 million improvement over the prior period in 2024. The adjusted earnings calculation does not include the benefit of the $0.6 million cost of goods for Vibativ and Sancuso during the quarter, which were received as part of each product's acquisition. Balance Sheet: At June 30, 2024, Cumberland had $78.5 million in total assets, including $17.3 million in cash and cash equivalents. Total liabilities were $52.5 million, including $16.1 million outstanding on the company's revolving line of credit. Total shareholders' equity was $26.3 million at the end of the quarter. EARNINGS REPORT CALL: A conference call will be held on August 6, 2024, at 4:30 p.m. Eastern Time to provide a Company update discuss the financial results. To participate in the call, please register at: . Registered participants can dial in from their phone using a dial-in and PIN number that will be provided to them. Alternatively, they can choose a "Call Me" option to have the system automatically call them at the start of the conference. A replay of the call will be available for one year and can be accessed via Cumberland's website or by visiting: . ABOUT CUMBERLAND PHARMACEUTICALS: Cumberland Pharmaceuticals Inc. is the largest biopharmaceutical company founded and headquartered in Tennessee and is focused on providing unique products that improve the quality of patient care. The company develops, acquires, and commercializes products for the hospital acute care, gastroenterology and oncology market segments. The company's portfolio of FDA-approved brands includes: Acetadote® (acetylcysteine) injection, for the treatment of acetaminophen poisoning; Caldolor® (ibuprofen) injection, for the treatment of pain and fever; Kristalose® (lactulose) oral, a prescription laxative, for the treatment of constipation; Sancuso® (granisetron) transdermal, 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; and 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. The company also has a series of Phase II clinical programs underway evaluating its ifetroban product candidate in patients with cardiomyopathy associated with Duchenne Muscular Dystrophy, Systemic Sclerosis and Idiopathic Pulmonary Fibrosis. For more information on Cumberland's approved products, including full prescribing information, please visit links to the individual product websites, which can be found on the company's website . About Acetadote® (acetylcysteine) Injection Acetadote, administered intravenously within 8 to 10 hours after ingestion of a potentially hepatotoxic quantity of acetaminophen, is indicated to prevent or lessen hepatic injury. Used in the emergency department, Acetadote is approved in the United States to treat overdose of acetaminophen, a common ingredient in many over-the-counter medications. Acetadote is contraindicated in patients with hypersensitivity or previous anaphylactoid reactions to acetylcysteine or any components of the preparation. For full prescribing and safety information, visit . About Caldolor® (ibuprofen) Injection Caldolor is indicated in adults and pediatric patients for the management of mild to moderate pain and management of moderate to severe pain as an adjunct to opioid analgesics, as well as the reduction of fever. It was the first FDA-approved intravenous therapy for fever. Caldolor is contraindicated in patients with known hypersensitivity to ibuprofen or other NSAIDs, patients with a history of asthma or other allergic type reactions after taking aspirin or other NSAIDs. Caldolor is contraindicated for use during the peri-operative period in the setting of coronary artery bypass graft (CABG) surgery. For full prescribing and safety information, including boxed warning, visit . About Kristalose® (lactulose) Oral Solution Kristalose is indicated for the treatment of acute and chronic constipation. It is a unique, proprietary, crystalline form of lactulose, with no restrictions on length of therapy or patient age. Kristalose is contraindicated in patients who require a low-galactose diet. Elderly, debilitated patients who receive lactulose for more than six months should have serum electrolytes (potassium, chloride, carbon dioxide) measured periodically. For full prescribing and safety information, visit . About Sancuso® (granisetron) Transdermal System Sancuso is the only skin patch approved by the FDA for the prevention of chemotherapy-induced nausea and vomiting ("CINV") in patients receiving moderately and/or highly emetogenic chemotherapy. When applied 24 to 48 hours before receiving chemotherapy, the Sancuso patch slowly and continuously releases the medicine contained in the adhesive through clean and intact skin areas into the patient's bloodstream. It can prevent CINV for chemotherapy regimens of up to five consecutive days. For full prescribing and safety information, visit . About Vaprisol® (conivaptan hydrochloride) Injection Vaprisol is an intravenous treatment for hyponatremia used in the critical care setting. Hyponatremia is an electrolyte disturbance in which sodium ion concentration in blood plasma is lower than normal. This can be associated with a variety of critical care conditions including congestive heart failure, liver failure, kidney failure and pneumonia. The product is a vasopressin receptor antagonist that raises serum sodium levels and promotes free water secretion. Vaprisol is contraindicated in patients with hypovolemic hyponatremia. The coadministration of Vaprisol with potent CYP3A inhibitors, such as ketoconazole, itraconazole, clarithromycin, ritonavir and indinavir, is contraindicated. For full prescribing and safety information, including boxed warning, visit . About Vibativ® (telavancin) Injection 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. Intravenous unfractionated heparin sodium is contraindicated with Vibativ administration due to artificially prolonged activated partial thromboplastin time (aPTT) test results for up to 18 hours after Vibativ administration. Vibativ is contraindicated in patients with a known hypersensitivity to telavancin. For more information, please visit . ABOUT CUMBERLAND EMERGING TECHNOLOGIES: Cumberland Emerging Technologies, Inc. () is a joint initiative between Cumberland Pharmaceuticals Inc., Vanderbilt University, LaunchTN and WinHealth. The mission of CET is to advance biomedical technologies and products conceived at Vanderbilt University and other regional research centers toward the marketplace. CET helps manage the development and commercialization process for select projects, and provides expertise on intellectual property, regulatory, manufacturing and marketing issues that are critical to successful new biomedical products. CET's Life Sciences Center provides laboratory space, equipment and infrastructure for CET's activities and other early-stage life sciences ventures. FORWARD LOOKING STATEMENTS: This press release contains forward-looking statements, which are subject to certain risks and reflect Cumberland's current views on future events based on what it believes are reasonable assumptions. No assurance can be given that these events will occur. Forward-looking statements include, among other things, statements regarding the company's intent, belief or expectations, and can be identified by the use of terminology such as "may," "will," "expect," "believe," "intend," "plan," "estimate," "should," "seek," "anticipate," "look forward" and other comparable terms or the negative thereof. As with any business, all phases of Cumberland's operations are subject to factors outside of its control, and any one or combination of these factors could materially affect Cumberland's operation results. These factors include macroeconomic conditions, including rising interest rates and inflation, competition, an inability of manufacturers to produce Cumberland's products on a timely basis, failure of manufacturers to comply with regulations applicable to pharmaceutical manufacturers, natural disasters, public health epidemics, maintaining an effective sales and marketing infrastructure, and other events beyond the company's control as more fully discussed in its most recent annual report on Form 10-K as filed with the U.S. Securities and Exchange Commission ("SEC"), as well as the company's other filings with the SEC from time to time. There can be no assurance that results anticipated by the company will be realized or that they will have the expected effects. Readers are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date hereof. The company does not undertake any obligation to publicly revise these statements to reflect events after the date hereof. The Company provided the above adjusted supplemental financial performance measures, which are considered "non-GAAP" financial measures under applicable SEC rules and regulations. These financial measures should be considered supplemental to, and not as a substitute for, financial information prepared in accordance with Generally Accepted Accounting Principles ("GAAP"). The definition of these supplemental measures may differ from similarly titled measures used by others. Because these supplemental financial measures exclude the effect of items that will increase or decrease the Company's reported results of operations, management encourages investors to review the Company's consolidated financial statements and publicly filed reports in their entirety. A reconciliation of the supplemental financial measures to the most directly comparable GAAP financial measures is included in the tables accompanying this release. Cumberland's management believes these supplemental financial performance measures are important as they are used by management, along with financial measures in accordance with GAAP, to evaluate the Company's operating performance. In addition, Cumberland believes that they will be used by certain investors to measure the Company's operating results. Management believes that presenting these supplemental measures provides useful information about the Company's underlying performance across reporting periods on a consistent basis by excluding items that Cumberland does not believe are indicative of its core business performance or reflect long-term strategic activities. Certain of these items are not settled through cash payments and include: depreciation, amortization, share-based compensation expense and income taxes. Cumberland utilizes its net operating loss carryforwards to pay minimal income taxes. In addition, the use of these financial measures provides greater transparency to investors of supplemental information used by management in its financial and operational decision-making, including the evaluation of the Company's operating performance. The Company defines these supplemental financial measures as follows: Adjusted Earnings (loss): net income (loss) adjusted for the impact of income taxes, depreciation and amortization expense, share-based compensation, interest income and interest expense. (a) Represents the share-based compensation of Cumberland. Adjusted Diluted Earnings (loss) Per Share: Adjusted Earnings (loss) divided by diluted weighted-average common shares outstanding. SOURCE Cumberland Pharmaceuticals Inc.