Paranasal Sinus Diseases

The FDA on Friday signed off on a new indication for Optinose’s nasal spray Xhance as a treatment for chronic rhinosinusitis without nasal polyps in adults. Xhance first won FDA approval in 2017 as a treatment for nasal polyps in adults, and its drug component first won approval in 1994. The drug-device combo product uses a proprietary delivery system with a common steroid, known as fluticasone propionate. Optinose said the approval was based on a large placebo-controlled trial that demonstrated a statistically significant reduction of symptoms in chronic sinusitis patients without nasal polyps. You’ll get access to free articles each month, plus you can customize what newsletters get delivered to your inbox each week, including breaking news.

ReOpen was the first ever large placebo-controlled clinical trial program to demonstrate statistically significant reduction of symptoms in chronic sinusitis patients without nasal polyps Clinical trial program also showed reduction in sinus inflammation and in acute exacerbations, which frequently result in use of antibiotics XHANCE uses the proprietary Exhalation Delivery System to enable deposition of a proven steroid in target areas of inflammation deep in the nose not typically reached by standard nasal sprays Chronic sinusitis affects approximately 30 million adults in the U.S. YARDLEY, Pa., March 15, 2024 (GLOBE NEWSWIRE) -- Optinose (NASDAQ:OPTN), a pharmaceutical company focused on patients treated by ear, nose and throat (ENT) and allergy specialists, today announced the U.S. Food and Drug Administration (FDA) has approved XHANCE® (fluticasone propionate) nasal spray for the treatment of chronic rhinosinusitis without nasal polyps in patients 18 years of age and older. Chronic sinusitis (also called “chronic rhinosinusitis” or “CRS”) is one of the most common chronic diseases, affecting approximately 30 million adults in the United States. Research shows that the disease impairs quality of life to a similar degree as other serious chronic conditions, such as chronic obstructive pulmonary disease, sciatica, or migraine. Chronic sinusitis is also one of the most common diagnoses in adult outpatient medicine. Chronic sinusitis is diagnosed in approximately 10 million outpatient visits, of which approximately 70% result in antibiotic prescriptions, and leads to more than 600,000 surgeries annually. Although there are FDA–approved medications to treat nasal polyps, including XHANCE, no medication had ever been approved for the more than two-thirds of chronic sinusitis patients who do not have nasal polyps – until today.1 “The FDA approval of XHANCE for the treatment of CRS without nasal polyps is an important milestone,” said Rick Chandra, M.D., Professor of Otolaryngology-Head and Neck Surgery, Endowed Director, Roland “Ron” Eavey, MD, SM Endowed Directorship in Leadership and Education, Service Chief, Rhinology and Skull Base Surgery, Vanderbilt University. “Until today, we have been forced to use unproven therapies to try and alleviate the symptoms that these patients suffer. While we often resort to using nasal steroid sprays in this patient population, they have never been shown to be effective in large placebo-controlled clinical studies. XHANCE, which uses the Exhalation Delivery System to enable delivery of an established topical steroid to the areas of the nasal cavity and sinuses we know to be extensively inflamed, is now proven to be effective in treating our CRS patients both with and without nasal polyps.” “People who don’t suffer from chronic sinusitis may not appreciate how burdensome the condition can be. More than 80% of patients with chronic sinusitis report frustration with symptom relief when using a standard-delivery nasal steroid sprays, and patients commonly use multiple unproven over the counter medications in an effort to find symptom relief.” said Ramy Mahmoud, MD, MPH, CEO of Optinose. “Although chronic sinusitis is one of the most common diagnoses in outpatient physician visits, and surgery is available, there has never been a prescription medication approved by the FDA as safe and effective to treat the millions of patients without nasal polyps suffering from this debilitating disease. We are thrilled to now be able to offer new hope to these patients and believe XHANCE has the potential to become part of the standard of care for the treatment of chronic sinusitis.” The approval was based on data from the ReOpen program evaluating XHANCE for treatment of adults with chronic sinusitis. A drug-device combination product, XHANCE uniquely combines a widely used nasal steroid with the Exhalation Delivery System™, an innovative delivery system designed to target the sites where inflammation occurs, especially difficult-to-access sinuses and sinonasal drainage tracts not typically reached by standard-delivery nasal sprays. The safety pro tolerability of XHANCE for patients in the ReOpen trials was generally consistent with its currently labeled safety profile. The most common adverse reactions (incidence ≥ 3%) in the ReOpen program were epistaxis, headache, and nasopharyngitis. About Optinose Optinose is a global specialty pharmaceutical company focused on serving the needs of patients cared for by ear, nose and throat (ENT) and allergy specialists. To learn more, please visit or follow us on X and LinkedIn. About XHANCE XHANCE® is a drug-device combination product that uses the Exhalation Delivery System™ (also referred to as the EDS®) designed to deliver a topical steroid to the high and deep regions of the nasal cavity where sinuses ventilate and drain. XHANCE is approved by the U.S. Food and Drug Administration for the treatment of chronic rhinosinusitis (with and without nasal polyps) in patients 18 years of age or older. About the ReOpen Program The ReOpen program comprised two global, randomized, double-blind, placebo-controlled Phase 3 trials that evaluated the efficacy and safety of one or two sprays of XHANCE in each nostril twice daily, over 24 weeks, in patients suffering from chronic sinusitis. In ReOpen1, the first of the two trials, 332 chronic sinusitis patients either with or without concurrent nasal polyps were treated. In ReOpen2, 222 chronic sinusitis patients who did not have polyps in the nasal cavity were treated. The co-primary endpoints were change from baseline in symptoms, as measured by composite symptom score (nasal congestion, facial pain or pressure, and nasal discharge) at the end of week 4, and change in inflammation inside the sinus cavities, as measured by CT scans (change in the average of the percentages of volume occupied by disease in the ethmoid and maxillary sinuses) at week 24. The ReOpen trial program is a landmark research program that included the first ever large, placebo-controlled trials we are aware of to demonstrate that any nasal medication produces significant improvement in both symptoms and inflammation inside the sinuses for patients with chronic sinusitis, regardless of whether or not nasal polyps are present, and to show reduction in the number of acute exacerbations.1 IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS: Hypersensitivity to any ingredient in XHANCE. WARNINGS AND PRECAUTIONS: Local nasal adverse reactions, including epistaxis, erosion, ulceration, septal perforation, Candida albicans infection, and impaired wound healing, can occur. Monitor patients periodically for signs of possible changes on the nasal mucosa. Avoid use in patients with recent nasal ulcerations, nasal surgery, or nasal trauma until healing has occurred. Glaucoma and cataracts may occur with long-term use. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use XHANCE long-term. Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, contact dermatitis, rash, hypotension, and bronchospasm) have been reported after administration of fluticasone propionate. Discontinue XHANCE if such reactions occur. Immunosuppression and infections can occur, including potential increased susceptibility to or worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infection; ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue XHANCE slowly. Assess for decrease in bone mineral density initially and periodically thereafter. ADVERSE REACTIONS: Chronic rhinosinusitis without nasal polyps: The most common adverse reactions (incidence ≥3%) are epistaxis, headache, and nasopharyngitis. Chronic rhinosinusitis with nasal polyps: The most common adverse reactions (incidence ≥3%) are epistaxis, nasal septal ulceration, nasopharyngitis, nasal mucosal erythema, nasal mucosal ulcerations, nasal congestion, acute sinusitis, nasal septal erythema, headache, and pharyngitis. DRUG INTERACTIONS: Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. May increase risk of systemic corticosteroid effects. USE IN SPECIFIC POPULATIONS: Hepatic impairment. Monitor patients for signs of increased drug exposure. Please see full Prescribing Information, including Instructions for Use References James N. Palmer, Nithin D. Adappa, Rakesh K. Chandra, Greg E. Davis, Mahboobeh Mahdavinia, John Messina, Randall A. Ow, Zara M. Patel, Anju T. Peters, Harry Sacks, Rodney J. Schlosser, Raj Sindwani, Zachary M. Soler, Andrew A. White, Sarah K. Wise, Ramy A. Mahmoud, Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2), The Journal of Allergy and Clinical Immunology: In Practice, 2024,, ISSN 2213-2198, ( ) Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements that are not historical facts are hereby identified as forward-looking statements for this purpose and include, among others, statements relating to the benefits of XHANCE for the treatment of chronic sinusitis (also called chronic rhinosinusitis) with and without nasal polyps; the benefits of the approval of XHANCE for the treatment of chronic rhinosinusitis without nasal polyps; the potential for XHANCE to become part of the standard of care for the treatment of chronic sinusitis; the benefits of the Exhalation Delivery System; and other statements regarding the Company's future operations, prospects, objectives, and other future events. Forward-looking statements are based upon management’s current expectations and assumptions and are subject to a number of risks, uncertainties and other factors that could cause actual results and events to differ materially and adversely from those indicated by such forward-looking statements including, among others: physician and patient acceptance of XHANCE for its new indication (treatment of adults with chronic rhinosinusitis without nasal polyps); the Company’s ability to maintain adequate third party reimbursement for XHANCE (including its new indication); potential for varying interpretation of clinical trial results of XHANCE for the treatment of chronic sinusitis; ; the prevalence of chronic sinusitis and market opportunities for XHANCE may be smaller than the Company expects; and the risks, uncertainties and other factors discussed under the caption "Item 1A. Risk Factors" and elsewhere in our most recent Form 10-K and Form 10-Q filings with the Securities and Exchange Commission - which are available at . As a result, you are cautioned not to place undue reliance on any forward-looking statements. Any forward-looking statements made in this press release speak only as of the date of this press release, and we undertake no obligation to update such forward-looking statements, whether as a result of new information, future developments or otherwise. Optinose Investor Contact Jonathan Neely jonathan.neely@optinose.com 267.521.0531

VANCOUVER, BC, March 13, 2024 /PRNewswire/ - In a recent presentation to the US Biophysical Society in Philadelphia1, Asep Medical Holdings Inc. ("Asep Inc." or the "Company") (CSE: ASEP) (OTCQB: SEPSF) (FSE: JJ8) CEO Dr. Bob Hancock announced how the ground-breaking use of artificial intelligence (AI) has allowed the development of new and improved treatments for biofilm infections. Biofilms are communities of bacteria that infect surfaces and cause 65% of all infections. They are very hard to treat, highly resistant to all antibiotics and no FDA-approved treatment for biofilms has been developed. Asep Medical's peptides have very potent activity against biofilms and thus have the potential to replace current sub-optimal treatments, including physical removal and combinations of antibiotics. Neural network artificial intelligence (AI) methods were applied to predict improved peptides based on the company's extensive stock of proprietary peptides and, in company-sponsored studies, have been shown to enable the prediction of improved peptides with substantially higher activity against biofilms2. This has allowed the company to enhance both activity and ability to suppress inflammation (the primary pathology of biofilm infections) and to explore the diverse markets impacted by biofilms, which cost global health care an estimated $368 billion annually3. These markets include oral health (dental) care4, wounds5 and chronic rhinosinusitis6, all addressed by Asep peptides that show excellent activity in model infections. Asep's first-generation product will be an oral irrigant/rinse for preventing biofilm infections in the oral cavity, which can lead to infections and erosion of teeth and dental implants. Another use for AI technology (LASSO regression) is in the development of the SepsetER blood-based gene expression test that is preparing to enter 510(k) regulatory approval studies in the USA. This test was developed at the University of British Columbia (UBC) under the guidance of Prof. Robert E. W. Hancock and analyzes the dysfunctional immune responses involved in sepsis7. Artificial intelligence8,9 was used to identify the minimum set of genes involved in a process termed cellular reprogramming (one of the types of immune dysfunction in sepsis), and it was shown that the expression of just 6 genes can accurately predict whether a patient will acquire sepsis and associated multi-organ failure. "We have harnessed AI to diagnose sepsis. Sepsis is a severe disease responsible for one in five deaths worldwide1 and essentially all deaths from pandemic microbes like COVID-19," says Dr. Hancock, Chair and CEO of Asep Inc. "It is critical to identify sepsis as early as possible due to the 7.6% increased risk of death10 for every hour of delay in diagnosis and initiation of appropriate treatment. No conventional assay exists that accurately predicts sepsis onset in the first hours after a patient enters the hospital. Asep scientists have found that SepsetER can predict whether a patient will subsequently acquire sepsis in 9 out of 10 patients in the ICU and 7 of 10 patients in the emergency department, based on analysis of company and published data". AI was also used to simplify the extreme complexity7 of sepsis, which has limited treatments to date. In clinical studies of patients from 4 countries/4 continents published by the Lancet Journal EBioMedicine8 and the Nature Journal Scientific Reports9, LASSO regression AI methods were applied. Five groupings (endotypes) of patients were identified as showing major differences in the underlying immune defects in each group8. These endotypes could be assessed using simple gene assays that were 89-97% accurate8. "Deciphering the underlying immune defects of sepsis patients is key to devising precision treatments tailored to the specific type of sepsis in patients," stated Asep CSO Dr. Evan Haney, "This will form the basis of a second test in development." OVERCOMING ANTIBIOTIC FAILURE The failure of antibiotics11 due to delayed diagnosis of sepsis, the high prevalence of recalcitrant biofilm infections and increased antibiotic resistance, compounded by declining antibiotic discovery, are among society's most pressing health issues. As described above, Dr. Hancock and his team have applied AI to discover a host of antimicrobial peptides (strings of a dozen or so amino acids), representing a promising new class of antibiotics. Asep Inc. has adapted these AI methods to address antibiotic failure associated with biofilms (a multi-cellular growth state of bacteria adaptively resistant to conventional antibiotics)12,13. Dr. Hancock's team used peptide array technology to prepare large random peptide libraries created using the amino acid composition of the most active peptides. The resultant data was used with an AI technique called artificial neural networks to develop quantitative in-silico models of antibiotic activity2,12. Random tests proved remarkably effective in predicting the activity of 100,000 virtual peptides. The best peptides, representing the top quartile of predicted activities, were effective against a broad array of multidrug-resistant "Superbugs" with activities that were equal to or better than four highly used conventional antibiotics, more effective than the most advanced clinical candidate antimicrobial peptide, and protective against Staphylococcus aureus infections in animal models. Similar methods were used to derive excellent antibiofilm peptides. Asep is preparing to take the best of these peptides to the clinic. "We use AI daily as a valuable tool in the battle against antibiotic failure to solve problems that have defied conventional methods. While others are trying to figure out how AI can be best used, we are already using it with amazing success in diagnostics and therapeutics. Asep Inc. is dedicated to leveraging AI's power to improve human health," said Dr. Evan Haney, Chief Scientific Officer of Asep. ABOUT ASEP MEDICAL HOLDINGS INC. Asep Medical Holdings Inc. (asepmedical.com) is dedicated to addressing the global issue of antibiotic failure by developing novel solutions for significant unmet medical needs in human medicine. The Company is a consolidation of three existing private companies, all with technology in advanced development — Sepset Biosciences Inc. (proprietary diagnostic tools to enable the early and timely identification of sepsis), ABT Innovations Inc. (broad-spectrum therapeutic agents to address multi-drug resistant biofilm infections), and SafeCoat Medical Inc. (an antimicrobial peptide, anti-fouling medical device coating technology). Sepset Biosciences Inc. (sepset.ca) is developing a diagnostic technology that involves a patient gene expression signature that predicts the development of severe sepsis, one of the significant diseases leading to antibiotic failure, since antibiotics are the primary treatment for sepsis. Sepsis was responsible for nearly 20% of all deaths on the planet in 2017 and essentially all deaths due to COVID-19 and other pandemics. The SepsetER test is a blood-based gene expression assay that is straightforward to implement, and results are obtained in about an hour after taking a blood sample in the emergency room or intensive care unit. This proprietary diagnostic technology differs from current diagnostic tests in enabling the diagnosis of severe sepsis within 60 minutes of initiating the test. Bacterial culture, the gold standard, provides a diagnosis after ~15 hours but can be as long as three days. Asep Inc. believes its test will enable physicians to make critical early decisions regarding appropriate therapies and thus reduce overall morbidity and mortality due to sepsis. ABT Innovations Inc.'s (abtinnovations.ca) peptide technology covers a broad range of therapeutic applications, including bacterial biofilm infections (medical device infections, chronic infections, lung, bladder, wound, dental, skin, ear-nose and throat, sinusitis, orthopaedic, etc.), anti-inflammatories, anti-infective immune-modulators and vaccine adjuvants. The company is in the pre-clinical development phase with promising data. SafeCoat Medical Inc.'s (safecoatmedical.com) technology incorporates self-assembling biocompatible polymers that can be combined with conjugated antimicrobial peptides and applied to virtually any surface as stable antimicrobial and/or anti-fouling coatings. Of particular interest is the application of this versatile antimicrobial coating to various medical devices and implants that often become contaminated with biofilm infections. SafeCoat is optimizing methods to manufacture and apply these anti-bacterial coatings to a host of surfaces and can tailor the composition of the coating and associated peptide sequences for any desired application. FORWARD-LOOKING STATEMENTS — This news release contains certain "forward-looking statements" within the meaning of such statements under applicable securities law. Forward-looking statements are frequently characterized by words such as "anticipates," "plan," "continue," "expect," "project," "intend," "believe," "anticipate," "estimate," "may," "will," "potential," "proposed," "positioned" and other similar words, or statements that certain events or conditions "may" or "will" occur. These statements include but are not limited to the successful clinical testing of our Sepsis diagnostic test and its intended filing for regulatory approval; the Company not receiving regulatory approval as planned or at all; the undertaking of pre-clinical studies on our lead therapeutic, with the expectation that this will lead to fast-track clinical trials; the timeframe for diagnosis of sepsis with the company's products; the potential opportunities for the generation of revenue; the therapeutic benefits of the company's products; and other statements regarding the company's proposed business plans. Various assumptions were used in drawing conclusions or making the predictions contained in the forward-looking statements throughout this news release. Forward-looking statements are based on the opinions and estimates of management at the date the statements are made and are subject to a variety of risks including the risk that the company's products may not perform as expected; that the company may not receive the requisite regulatory approvals or results of testing; the Company's testing of the products may not be successful and approvals may not be obtained in the estimated timelines or at all; the company may not be able to generate revenue from its products as expected or at all; the market for the company's products may not be as described in this news release; and various other risk factors identified in the Asep Medical Inc.'s prospectus dated November 9, 2021, and in the company's management discussion and analysis, available for review under the Company's profile at and uncertainties and other factors that could cause actual events or results to differ materially from those projected in the forward-looking statements. Asep Medical Inc. is under no obligation and expressly disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as expressly required by applicable law. ENDNOTES SOURCE ASEP Medical Holdings Inc.