Osteogenesis Imperfecta, Type 2A

Launching in December for Constipation Awareness Month, Initiatives Include Partnerships with Well-Known Lifestyle and Health Care Practitioner Influencers Campaign Coincides with Salix's Continued Support of Advocacy Groups Building Innovative Patient Education Programs and Advancing Disease State Research in 2023 LAVAL, QC / ACCESSWIRE / December 1, 2022 / Salix Pharmaceuticals, Ltd. ("Salix"), the gastroenterology business of Bausch Health Companies Inc. (NYSE:BHC)(TSX:BHC) ("Bausch Health"), today announced the launch of a series of social media and digital initiatives to raise awareness during Constipation Awareness Month in December. The initiatives will discuss constipation diseases, including opioid-induced constipation (OIC), irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC). It is estimated that approximately up to 80% of patients receiving opioid medications for chronic pain experience OIC,1 30 million adults have CIC,2,3 and 3.4 million have IBS-C.2,3 The initiatives launching this month culminate a year in which Salix invested in a multipronged educational campaign that included the publication of digital content reaching more than 240 million consumers with valuable information about the symptoms of OIC, IBS-C, and CIC and treatment options they can discuss with their health care providers. Constipation Awareness Month initiatives included partnerships with Johanna Grange, a lifestyle influencer who is sharing her perspectives about living with IBS-C with her 73,000 Instagram followers and in her blog, and Ethan Melillo, a pharmacist with more than 189,000 TikTok followers, who over the past year has been working with Salix to share a series of informative videos on TikTok discussing OIC and treatment options. "As an industry leader in the gastroenterology space, Salix is continually identifying innovative ways to connect with the patient communities we serve," said Nicola Kayel, vice president, Gastroenterology Marketing, Salix. "In 2022, in addition to continuing to work with social media influencers lending their voice to raise awareness of gastrointestinal (GI) diseases, Salix became the first organization to partner with the creators of the PLOP app, a new and creative bowel movement tracker digital solution that monitors and analyzes daily symptoms. The collaboration, which raises awareness about the connection between opioid pain medications and constipation, supports valuable conversations between patients and health care providers that may help lead to improved regularity in bowel movements." To further support patients with chronic GI disorders in 2023, Salix will extend its partnerships with prestigious patient advocacy groups to advance public awareness and education for patients and health care providers. Salix will continue its collaboration with the International Foundation for Gastrointestinal Disorders (IFFGD), the U.S. Pain Foundation, the American Chronic Pain Association (ACPA), and the American College of Emergency Physicians (ACEP). Through its 2023 medical grant contributions program, Salix will continue to work with organizations such as the American Gastroenterological Association (AGA) to advance research that will improve understanding of GI conditions. Salix will continue to host patient resources at UnderstandingOIC.com and ConfrontConstipation.com which also offer information about treatment options to be discussed with health care providers. About Salix Salix Pharmaceuticals is one of the largest specialty pharmaceutical companies in the world committed to the prevention and treatment of gastrointestinal diseases. For more than 30 years, Salix has licensed, developed and marketed innovative products to improve patients' lives and arm health care providers with life-changing solutions for many chronic and debilitating conditions. Salix currently markets its product line to U.S. health care providers through an expanded sales force that focuses on gastroenterology, hepatology, pain specialists and primary care. Salix is headquartered in Bridgewater, New Jersey. For more information about Salix, visit and connect with us on Twitter and LinkedIn. About Bausch Health Bausch Health Companies Inc. (NYSE/TSX: BHC) is a global diversified pharmaceutical company whose mission is to improve people's lives with our health care products. We develop, manufacture and market a range of products primarily in gastroenterology, hepatology, neurology, dermatology, international pharmaceuticals and eye health, through our controlling ownership interest in Bausch + Lomb. With our leading durable brands, we are delivering on our commitments as we build an innovative company dedicated to advancing global health. For more information, visit and connect with us on Twitter and LinkedIn. Forward-looking Statements This news release may contain forward-looking statements about the future performance of Bausch Health including the proposed plan to fully separate its eye health business, including the timing thereof, which may generally be identified by the use of the words "anticipates," "hopes," "expects," "intends," "plans," "should," "could," "would," "may," "believes," "subject to" and variations or similar expressions. These statements are based upon the current expectations and beliefs of management and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Actual results are subject to other risks and uncertainties that relate more broadly to Bausch Health's overall business, including those more fully described in Bausch Health's most recent annual report on Form 10-K and detailed from time to time in Bausch Health's other filings with the U.S. Securities and Exchange Commission and the Canadian Securities Administrators, which factors are incorporated herein by reference. ### ©2022 Salix Pharmaceuticals or its affiliates. SAL.0120.USA.22 1 Bell TJ, Panchal SJ, Miaskowski C, Bolge SC, Milanova T, Williamson R. The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1). Pain Med. 2009;10(1):35-42. doi:10.1111/j.1526-4637.2008.00495.x 2 Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Gastroenterology. 2021;160(1):99-114.e3. doi:10.1053/j.gastro.2020.04.014 3 Bureau USC. National Demographic Analysis Tables: 2020. Census.gov. . Published March 10, 2022. Accessed November 22, 2022. Investor Contact: Christina Cheng ir@bauschhealth.com (514) 856-3855 (877) 281-6642 (toll free) Media Contact: Kevin Wiggins corporate.communications@bauschhealth.com (908) 541-3785 Gianna Scalera salixcommunications@bauschhealth.com (908) 541-2110 SOURCE: Salix Pharmaceuticals View source version on accesswire.com:

Research Findings for XIFAXAN® (rifaximin), TRULANCE® (plecanatide) and RELISTOR® (methylnaltrexone bromide) Will be Presented LAVAL, Quebec, Oct. 25, 2021 /PRNewswire/ -- Bausch Health Companies Inc. (NYSE/TSX: BHC) ("Bausch Health") and its gastroenterology business, Salix Pharmaceuticals, Ltd. ("Salix"), one of the largest specialty pharmaceutical companies in the world committed to the treatment of gastrointestinal (GI) diseases and conditions, today announced seven posters featuring new data for XIFAXAN® (rifaximin), TRULANCE® (plecanatide) and RELISTOR® (methylnaltrexone bromide) are being presented at the American College of Gastroenterology® (ACG) 2021 Annual Scientific Meeting, which is taking place Oct. 22-27, 2021 in Las Vegas. "Salix is pleased to present important new clinical data on three key products in our gastrointestinal portfolio at ACG's annual scientific meeting," said Robert Spurr, president, Salix Pharmaceuticals. "We are especially excited to have the opportunity to connect in person with the gastroenterology community to collaborate on improving the well-being of patients living with various GI disorders." The complete list of Salix research being featured at ACG 2021 includes: XIFAXAN Bajaj, Jasmohan et al. "Rifaximin Plus Lactulose is More Efficacious than Lactulose Alone for Risk Reduction of Overt Hepatic Encephalopathy (OHE) Recurrence: a Subgroup Analysis by Viral or Alcohol Cirrhosis Etiology." Volk, Michael et al. "Emergency Department Utilization in Patients with Hepatic Encephalopathy (HE) Treated with Rifaximin (± Lactulose) Versus Lactulose Alone." TRULANCE Brenner, Darren et al. "Plecanatide Provided Clinically Meaningful Improvements in Health-Related Quality of Life in Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation: A Post Hoc Analysis." Harris, Lucinda et al. "Plecanatide Improved Stool Consistency in Patients With Chronic Idiopathic Constipation Regardless of Baseline BSFS: A Post Hoc Analysis." Sayuk, Gregory et al. "Plecanatide Improves Abdominal Symptoms in Individuals with Irritable Bowel Syndrome With Constipation and Chronic Idiopathic Constipation Including Those Experiencing Severe Bloating, Pain, and Discomfort." Shah, Eric et al. "Plecanatide Produces a More Rapid and Durable Clinical Response Compared to Placebo in Patients with Chronic Idiopathic Constipation: A Post-Hoc Analysis of Two Randomized Controlled Trials." RELISTOR Sayuk, Gregory et al. "A Pooled Analysis of the Efficacy and Safety of Methylnaltrexone for Opioid-Induced Constipation in Patients With Advanced Illness: Impact of Baseline Opioid Equivalent Dose." About XIFAXAN® Indications XIFAXAN® (rifaximin) 550 mg tablets are indicated for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults and for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults. IMPORTANT SAFETY INFORMATION XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis. Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. There is an increased systemic exposure in patients with severe (Child-Pugh Class C) hepatic impairment. Caution should be exercised when administering XIFAXAN to these patients. Caution should be exercised when concomitant use of XIFAXAN and P-glycoprotein (P-gp) and/or OATPs inhibitors is needed. Concomitant administration of cyclosporine, an inhibitor of P-gp and OATPs, significantly increased the systemic exposure of rifaximin. In patients with hepatic impairment, a potential additive effect of reduced metabolism and concomitant P-gp inhibitors may further increase the systemic exposure to rifaximin. In clinical studies, the most common adverse reactions for XIFAXAN were: HE (≥10%): Peripheral edema (15%), nausea (14%), dizziness (13%), fatigue (12%), and ascites (11%) IBS-D (≥2%): Nausea (3%), ALT increased (2%) INR changes have been reported in patients receiving rifaximin and warfarin concomitantly. Monitor INR and prothrombin time. Dose adjustment of warfarin may be required. XIFAXAN may cause fetal harm. Advise pregnant women of the potential risk to a fetus. To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or . Please click here for full Prescribing Information. About TRULANCE Indication Trulance (plecanatide) 3 mg tablets is indicated in adults for the treatment of Chronic Idiopathic Constipation (CIC) and Irritable Bowel Syndrome with Constipation (IBS-C). IMPORTANT SAFETY INFORMATION Contraindications Trulance is contraindicated in patients less than 6 years of age due to the risk of serious dehydration. Trulance is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Warnings and Precautions Risk of Serious Dehydration in Pediatric Patients Trulance is contraindicated in patients less than 6 years of age. The safety and effectiveness of Trulance in patients less than 18 years of age have not been established. In young juvenile mice (human age equivalent of approximately 1 month to less than 2 years), plecanatide increased fluid secretion as a consequence of stimulation of guanylate cyclase-C (GC-C), resulting in mortality in some mice within the first 24 hours, apparently due to dehydration. Due to increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than older patients to develop severe diarrhea and its potentially serious consequences. Use of Trulance should be avoided in patients 6 years to less than 18 years of age. Although there were no deaths in older juvenile mice, given the deaths in young mice and the lack of clinical safety and efficacy data in pediatric patients, use of Trulance should be avoided in patients 6 years to less than 18 years of age. Diarrhea Diarrhea was the most common adverse reaction in the four placebo-controlled clinical trials for CIC and IBS-C. Severe diarrhea was reported in 0.6% of Trulance-treated CIC patients, and in 1% of Trulance-treated IBS-C patients. If severe diarrhea occurs, the health care provider should suspend dosing and rehydrate the patient. Adverse Reactions In the two combined CIC clinical trials, the most common adverse reaction in Trulance-treated patients (incidence ≥2% and greater than in the placebo group) was diarrhea (5% vs 1% placebo). In the two combined IBS-C clinical trials, the most common adverse reaction in Trulance-treated patients (incidence ≥2% and greater than in the placebo group) was diarrhea (4.3% vs 1% placebo). Please also see the full Prescribing Information, including BOXED Warning, for additional risk information. About RELISTOR RELISTOR® (methylnaltrexone bromide) is an opioid antagonist. RELISTOR tablets and RELISTOR injection are indicated for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. RELISTOR injection is also indicated for the treatment of OIC in adults with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care. RELISTOR is not indicated to reduce all-cause mortality for opioid-induced bowel disorders. IMPORTANT SAFETY INFORMATION RELISTOR tablets and injection are contraindicated in patients with known or suspected mechanical gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation. Cases of gastrointestinal perforation have been reported in adult patients with opioid-induced constipation and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie's syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit pro using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn's disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom. If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their health care provider. Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia and should be monitored for adequacy of analgesia and symptoms of opioid withdrawal. Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal. The use of RELISTOR during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood-brain barrier and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because of the potential for serious adverse reactions, including opioid withdrawal, in breastfed infants, advise women that breastfeeding is not recommended during treatment with RELISTOR. In nursing mothers, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. A dosage reduction of RELISTOR tablets and RELISTOR injection is recommended in patients with moderate and severe renal impairment (creatinine clearance less than 60 mL/minute as estimated by Cockcroft-Gault). No dosage adjustment of RELISTOR tablets or RELISTOR injection is needed in patients with mild renal impairment. A dosage reduction of RELISTOR tablets is recommended in patients with moderate (Child-Pugh Class B) or severe (Child- Pugh Class C) hepatic impairment. No dosage adjustment of RELISTOR tablets is needed in patients with mild hepatic impairment (Child-Pugh Class A). No dosage adjustment of RELISTOR injection is needed for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, monitor for methylnaltrexone-related adverse reactions and dose adjust per Prescribing Information as may be indicated. In the clinical studies, the most common adverse reactions were: OIC in adult patients with chronic non-cancer pain RELISTOR tablets (≥ 2% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (14%), diarrhea (5%), headache (4%), abdominal distention (4%), vomiting (3%), hyperhidrosis (3%), anxiety (2%), muscle spasms (2%), rhinorrhea (2%), and chills (2%). RELISTOR injection (≥ 1% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (21%), nausea (9%), diarrhea (6%), hyperhidrosis (6%), hot flush (3%), tremor (1%), and chills (1%). OIC in adult patients with advanced illness RELISTOR injection (≥ 5% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (29%) flatulence (13%), nausea (12%), dizziness (7%), and diarrhea (6%). To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800- FDA-1088 or Please click here for full Prescribing Information for RELISTOR tablets and RELISTOR injection. About Salix Salix Pharmaceuticals is one of the largest specialty pharmaceutical companies in the world committed to the prevention and treatment of gastrointestinal diseases. For more than 30 years, Salix has licensed, developed and marketed innovative products to improve patients' lives and arm health care providers with life-changing solutions for many chronic and debilitating conditions. Salix currently markets its product line to U.S. health care providers through an expanded sales force that focuses on gastroenterology, hepatology, pain specialists and primary care. Salix is headquartered in Bridgewater, New Jersey. For more information about Salix, visit and connect with us on Twitter and LinkedIn. About Bausch Health Bausch Health Companies Inc. (NYSE/TSX: BHC) is a global company whose mission is to improve people's lives with our health care products. We develop, manufacture and market a range of pharmaceutical, medical device and over-the-counter products, primarily in the therapeutic areas of eye health, gastroenterology and dermatology. We are delivering on our commitments as we build an innovative company dedicated to advancing global health. For more information, visit and connect with us on Twitter and LinkedIn. Forward-looking Statements This news release may contain forward-looking statements, which may generally be identified by the use of the words "anticipates," "hopes," "expects," "intends," "plans," "should," "could," "would," "may," "believes," "estimates," "potential," "target," or "continue" and variations or similar expressions. These statements are based upon the current expectations and beliefs of management and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. These risks and uncertainties include, but are not limited to, the risks and uncertainties discussed in the Bausch Health Companies Inc.'s (Bausch Health) most recent annual report on Form 10-K and detailed from time to time in Bausch Health's other filings with the U.S. Securities and Exchange Commission and the Canadian Securities Administrators, which factors are incorporated herein by reference. They also include, but are not limited to, risks and uncertainties caused by or relating to the evolving COVID-19 pandemic, and the fear of that pandemic and its potential effects, the severity, duration, and future impact of which are highly uncertain and cannot be predicted, and which may have a material adverse impact on Bausch Health, including but not limited to its project development timelines, and costs (which may increase). Readers are cautioned not to place undue reliance on any of these forward-looking statements. These forward-looking statements speak only as of the date hereof. Bausch Health undertakes no obligation to update any of these forward-looking statements to reflect events or circumstances after the date of this news release or to reflect actual outcomes, unless required by law. ©2021 Salix Pharmaceuticals or its affiliates. TRULANCE and RELISTOR are trademarks of Salix Pharmaceuticals or its affiliates. The XIFAXAN 550 mg product and the XIFAXAN trademark are licensed by Alfasigma S.p.A. to Salix Pharmaceuticals or its affiliates. SAL.0138.USA.21 Company Codes: NYSE:BHC, Toronto:BHC

Two new analyses evaluate pharmacological and clinical advantages of Talicia® as first-line H. pylori therapy over clarithromycin-based regimens Two new analyses of Movantik® data evaluate efficacy in treating extreme opioid-induced constipation with severe symptoms Talicia®, an FDA approved therapy, is designed to replace clarithromycin-based regimens as first-line H. pylori eradication therapy; ACG Guideline recommends avoiding treatment with clarithromycin to eradicate H. pylori due to growing bacterial resistance Movantik is the U.S. market-leading oral peripherally acting mu-opioid receptor antagonist (PAMORA), approved to treat opioid-induced constipation in adults with chronic non-cancer pain [25-October-2021] TEL AVIV, Israel and RALEIGH, N.C., Oct. 25, 2021 /PRNewswire/ -- RedHill Biopharma (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, today announced the presentation of four new analyses of Phase 3 Talicia® (omeprazole magnesium, amoxicillin and rifabutin)[1] and Movantik® (naloxegol)[2] data at the ACG 2021 Annual Scientific Meeting, taking place October 22-27, 2021. The first Talicia analysis evaluated physician-directed therapy data, confirming high utilization of clarithromycin and low rates of H. pylori eradication. Inappropriate use of clarithromycin persists despite American College of Gastroenterology (ACG) recommendations to avoid clarithromycin when treating H. pylori patients who have a history of macrolide exposure, where local resistance rates are ≥ 15% or unknown, and/or when the patient has been previously treated with a clarithromycin-containing regimen. Utilization data based on U.S. prescriptions confirmed that clarithromycin-based regimens remain predominant, even though the majority of Americans have previously been prescribed a macrolide antibiotic[3]. The authors conclude that since Talicia does not contain clarithromycin, and resistance to amoxicillin and rifabutin is very rare, Talicia can be used first-line with minimal concern for antibiotic resistance or CYP2C19 metabolism. The second Talicia analysis assessed gastric luminal rifabutin concentrations of three times a day rifabutin 50 mg (the dose of rifabutin within Talicia®) vs. once-daily administration of rifabutin 150 mg, and the potential impact on H. pylori eradication. The data suggest that there may be a link between sustained gastric rifabutin exposure achieved with Talicia's unique dosing and formulation and the 90% eradication rates seen in clinical studies. The findings demonstrate that rifabutin dosed once-daily as 150 mg cannot replicate both the pharmacokinetic pro therapeutic effects of rifabutin 50 mg three-times daily (as dosed in Talicia®). "Sustained high intragastric rifabutin concentrations explain the high clinical trial eradication rates seen with Talicia and suggest that three-times daily Talicia should be considered a first-line therapy for patients with H. pylori infection." said Dr. Colin W. Howden, MD, AGAF, FACG, Professor Emeritus, University of Tennessee Health Science Center. "Contrary to ACG guideline recommendations, many physicians continue to prescribe clarithromycin-based therapies to patients, resulting in low rates of eradication because of high rates of clarithromycin resistance." The two Movantik posters analyzed data from patients experiencing extreme opioid-induced constipation (OIC) with severe symptoms. Both Movantik 12.5 mg and 25 mg provided rapid onset with early symptom relief and consistent, predictable and sustained efficacy in improving multiple symptoms despite high baseline symptom burden. Movantik also demonstrated a favorable safety-pro tolerability. The two analyses included pooled data from two large, pivotal Phase 3 studies of Movantik (Kodiak 4 and Kodiak 5; NCT01309841/NCT01323790), involving 891 treated patients across two doses (12.5 mg and 25 mg), compared to a total of 446 patients in the placebo arms. "Chronic pain patients are already subject to considerable suffering. For up to 80% of them, this is compounded by opioid-induced constipation – with a significant number suffering from extreme OIC with severe and debilitating symptoms. Movantik demonstrated both rapid and durable symptom improvement which are highly important clinical considerations in patients with OIC" said Dr. Darren M. Brenner, MD, AGAF, Associate Professor of Medicine and Surgery at Northwestern University Feinberg School of Medicine and Director of the Gastrointestinal Physiology Laboratory and Functional Bowel Programs. Posters Presented at ACG 2021 Annual Scientific Meeting: Talicia: Poster number 2029 RHB-105 Q8H Rifabutin Dosing Provides Favorable Exposure for Helicobacter pylori Eradication Presenter: Dr. Colin W. Howden Authors: Colin W. Howden, Salil N. Pendse, Mark A. Bush, June S. Almenoff, Kely L. Sheldon Poster number 3083 Pitfalls of Physician-Directed Treatment of Helicobacter pylori Infection: Results from Two Phase 3 Clinical Trials and Real-World Prescribing Data Presenter: Dr. Colin W. Howden Authors: Colin W. Howden, Kely L. Sheldon, June S. Almenoff, William D. Chey Movantik: Poster number 0386 Naloxegol Accelerates Time to First Spontaneous Bowel Movement (SBM) and Complete SBM (CSBM) with Predictable Efficacy in Patients with Extreme Opioid-Induced Constipation (OIC): A Pooled Analysis of Two Phase 3 Trials Presenter: Dr. Darren M. Brenner Authors: William Chey, Carol B. Rockett, Jeremy Adler, Theresa Mallick-Searle, Enoch Bortey, Darren M. Brenner Poster number 0397 Naloxegol Achieved Rapid and Sustained Improvement of Opioid-Induced Constipation (OIC) Symptoms in Patients with Extreme OIC: A Pooled Analysis of Two Pivotal Phase 3 Trials Presenter: Dr. Darren M. Brenner Authors: Darren M. Brenner, Carol B. Rockett, Jeremy Adler, Theresa Mallick-Searle, Enoch Bortey, William Chey About Talicia® Talicia® is the only rifabutin-based therapy approved for the treatment of H. pylori infection and is designed to address the high resistance of H. pylori bacteria to clarithromycin-based therapies. The high rates of H. pylori resistance to clarithromycin have led to significant rates of treatment failure with clarithromycin-based therapies and are a strong public health concern, as highlighted by the ACG, FDA and the World Health Organization (WHO) in recent years. Talicia® is a novel, fixed-dose, all-in-one oral capsule combination of two antibiotics (amoxicillin and rifabutin) and a proton pump inhibitor (PPI) (omeprazole). In November 2019, Talicia® was approved by the U.S. FDA for the treatment of H. pylori infection in adults. In the pivotal Phase 3 study, Talicia® demonstrated 84% eradication of H. pylori infection in the intent-to-treat (ITT) group vs. 58% in the active comparator arm (p<0.0001). Minimal to zero resistance to rifabutin, a key component of Talicia®, was detected in RedHill's pivotal Phase 3 study. Further, in an analysis of data from this study, it was observed that subjects who were confirmed adherent[4] to their therapy had response rates of 90.3% in the Talicia® arm vs. 64.7% in the active comparator arm[5]. Talicia® is eligible for a total of eight years of U.S. market exclusivity under its Qualified Infectious Disease Product (QIDP) designation and is also covered by U.S. patents which extend patent protection until 2034 with additional patents and applications pending and granted in various territories worldwide. About H. pylori H. pylori is a bacterial infection that affects approximately 35%[6] of the U.S. population, with an estimated two million patients treated annually[7]. Worldwide, more than 50% of the population has H. pylori infection, which is classified by the WHO as a Group 1 carcinogen. It remains the strongest known risk factor for gastric cancer[8] and a major risk factor for peptic ulcer disease[9] and gastric mucosa-associated lymphoid tissue (MALT) lymphoma[10]. More than 27,000 Americans are diagnosed with gastric cancer annually[11]. Eradication of H. pylori is becoming increasingly difficult, with current therapies failing in approximately 25-40% of patients who remain H. pylori-positive due to high resistance of H. pylori to antibiotics – especially clarithromycin – which is still commonly used in standard combination therapies[12]. About RedHill Biopharma RedHill Biopharma Ltd. (Nasdaq: RDHL) is a specialty biopharmaceutical company primarily focused on gastrointestinal and infectious diseases. RedHill promotes the gastrointestinal drugs, Movantik® for opioid-induced constipation in adults[13], Talicia® for the treatment of Helicobacter pylori (H. pylori) infection in adults[14], and Aemcolo® for the treatment of travelers' diarrhea in adults[15]. RedHill's key clinical late-stage development programs include: (i) RHB-204, with an ongoing Phase 3 study for pulmonary nontuberculous mycobacteria (NTM) disease; (ii) opaganib (ABC294640), a first-in-class oral SK2 selective inhibitor targeting multiple indications with a Phase 2/3 program for COVID-19 and Phase 2 studies for prostate cancer and cholangiocarcinoma ongoing; (iii) RHB-107 (upamostat), an oral serine protease inhibitor in a U.S. Phase 2/3 study as treatment for symptomatic COVID-19, and targeting multiple other cancer and inflammatory gastrointestinal diseases; (iv) RHB-104, with positive results from a first Phase 3 study for Crohn's disease; (v) RHB-102 , with positive results from a Phase 3 study for acute gastroenteritis and gastritis and positive results from a Phase 2 study for IBS-D; and (vi) RHB-106, an encapsulated bowel preparation. More information about the Company is available at / . About Talicia® (omeprazole magnesium, amoxicillin and rifabutin) INDICATION AND USAGE Talicia is a three-drug combination of omeprazole, a proton pump inhibitor, amoxicillin, a penicillin-class antibacterial, and rifabutin, a rifamycin antibacterial­­, indicated for the treatment of Helicobacter pylori infection in adults. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Talicia and other antibacterial drugs, Talicia should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. IMPORTANT SAFETY INFORMATION Talicia contains omeprazole, a proton pump inhibitor (PPI), amoxicillin, a penicillin-class antibacterial and rifabutin, a rifamycin antibacterial. It is contraindicated in patients with known hypersensitivity to any of these medications, any other components of the formulation, any other beta-lactams or any other rifamycin. Talicia is contraindicated in patients receiving rilpivirine-containing products. Talicia is contraindicated in patients receiving delavirdine or voriconazole. Serious and occasionally fatal hypersensitivity reactions have been reported with omeprazole, amoxicillin and rifabutin. Severe cutaneous adverse reactions (SCAR) (e.g. Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN)) have been reported with rifabutin, amoxicillin, and omeprazole. Additionally, drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported with rifabutin. Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range from mild diarrhea to fatal colitis. Talicia may cause fetal harm. Talicia is not recommended for use in pregnancy. Talicia may reduce the efficacy of hormonal contraceptives. An additional non-hormonal method of contraception is recommended when taking Talicia. Talicia should not be used in patients with hepatic impairment or severe renal impairment. Acute Interstitial Nephritis has been observed in patients taking PPIs and penicillins. Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs. These events have occurred as both new onset and exacerbation of existing autoimmune disease. The most common adverse reactions (≥1%) were diarrhea, headache, nausea, abdominal pain, chromaturia, rash, dyspepsia, oropharyngeal pain, vomiting, and vulvovaginal candidiasis. To report SUSPECTED ADVERSE REACTIONS, contact RedHill Biopharma INC. at 1-833-ADRHILL (1-833-237-4455) or FDA at 1-800-FDA-1088 or . Full prescribing information for Talicia is available at About Movantik® (naloxegol) Movantik® is an opioid antagonist indicated for the treatment of opioidinduced constipation (OIC) in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. Important Safety Information About Movantik Movantik® (naloxegol) is contraindicated in: Patients with known or suspected gastrointestinal (GI) obstruction and patients at risk of recurrent obstruction, due to the potential for GI perforation. Patients receiving strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) because these medications can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms. Patients with a known serious or severe hypersensitivity reaction to Movantik or any of its excipients. Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning, occurred in patients treated with Movantik. Patients receiving methadone as therapy for their pain condition were observed in the clinical trials to have a higher frequency of GI adverse reactions that may have been related to opioid withdrawal than patients receiving other opioids. Patients with disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal or reduced analgesia. These patients (e.g., multiple sclerosis, recent brain injury, Alzheimer's disease, and uncontrolled epilepsy) were not enrolled in the clinical studies. Take into account the overall risk-benefit pro using Movantik in such patients. Monitor for symptoms of opioid withdrawal when using Movantik in such patients. Severe abdominal pain and/or diarrhea have been reported, generally within a few days of initiation of Movantik. Monitor and discontinue if severe symptoms occur. Consider restarting Movantik at 12.5 mg once daily. Cases of GI perforation have been reported with the use of peripherally acting opioid antagonists, including Movantik. Postmarketing cases of GI perforation, including fatal cases, were reported when Movantik was used in patients at risk of GI perforation (e.g., infiltrative gastrointestinal tract malignancy, recent gastrointestinal tract surgery, diverticular disease including diverticulitis, ischemic colitis, or concomitantly treated with bevacizumab). Monitor for severe, persistent, or worsening abdominal pain; discontinue if this symptom develops. The most common adverse reactions with Movantik as compared to placebo in clinical trials were: Abdominal pain (21% vs 7%), diarrhea (9% vs 5%), nausea (8% vs 5%), flatulence (6% vs 3%), vomiting (5% vs 4%), headache (4% vs 3%), and hyperhidrosis (3% vs <1%). Movantik (naloxegol) is indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. Click here for the Medication Guide and full Prescribing Information for Movantik. You are encouraged to report Adverse Reactions to RedHill Biopharma Inc. at 1-833-ADRHILL (1-833-237-4455) or FDA at 1-800-FDA-1088 or . MOVANTIK is a registered trademark of the AstraZeneca group of companies. This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements may be preceded by the words "intends," "may," "will," "plans," "expects," "anticipates," "projects," "predicts," "estimates," "aims," "believes," "hopes," "potential" or similar words. Forward-looking statements are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company's control and cannot be predicted or quantified, and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company's research, manufacturing, pre-clinical studies, clinical trials, and other therapeutic candidate development efforts, and the timing of the commercial launch of its commercial products and ones it may acquire or develop in the future; (ii) the Company's ability to advance its therapeutic candidates into clinical trials or to successfully complete its pre-clinical studies or clinical trials or the development of a commercial companion diagnostic for the detection of MAP; (iii) the extent and number and type of additional studies that the Company may be required to conduct and the Company's receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company's therapeutic candidates and Talicia®; (v) the Company's ability to successfully commercialize and promote Talicia®, and Aemcolo® and Movantik®; (vi) the Company's ability to establish and maintain corporate collaborations; (vii) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (viii) the interpretation of the properties and characteristics of the Company's therapeutic candidates and the results obtained with its therapeutic candidates in research, pre-clinical studies or clinical trials; (ix) the implementation of the Company's business model, strategic plans for its business and therapeutic candidates; (x) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (xi) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; (xii) estimates of the Company's expenses, future revenues, capital requirements and needs for additional financing; (xiii) the effect of patients suffering adverse experiences using investigative drugs under the Company's Expanded Access Program; (xiv) competition from other companies and technologies within the Company's industry; and (xv) the hiring and employment commencement date of executive managers. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on March 18, 2021. All forward-looking statements included in this press release are made only as of the date of this press release. The Company assumes no obligation to update any written or oral forward-looking statement, whether as a result of new information, future events or otherwise unless required by law. [1] Talicia® (omeprazole magnesium, amoxicillin and rifabutin) delayed-release capsules 10 mg/250 mg/12.5 mg is indicated for the treatment of Helicobacter pylori (H. pylori) infection in adults. For full prescribing information see: . [2] Full prescribing information for Movantik® (naloxegol) is available at: . [3] Centers for Disease Control and Prevention (CDC) – antibiotic prescribing and use, outpatient antibiotic prescriptions. [4] Defined as the PK population which included those subjects in the ITT population who had demonstrated presence of any component of investigational drug at visit 3 (approx. day 13) or had undetected levels drawn >250 hours after the last dose. [5] The pivotal Phase 3 study with Talicia® demonstrated 84% eradication of H. pylori infection with Talicia® vs. 58% in the active comparator arm (ITT analysis, p<0.0001). [6] Hooi JKY et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology 2017; 153:420-429. [7] IQVIA Custom Study for RedHill Biopharma, 2019 [8] Lamb A et al. Role of the Helicobacter pylori–Induced inflammatory response in the development of gastric cancer. J Cell Biochem 2013;114.3:491-497. [9] NIH – Helicobacter pylori and Cancer, September 2013. [10] Hu Q et al. Gastric mucosa-associated lymphoid tissue lymphoma and Helicobacter pylori infection: a review of current diagnosis and management. Biomarker research 2016;4.1:15. [11] National Cancer Institute, Surveillance, Epidemiology, and End Results Program (SEER). [12] Malfertheiner P. et al. Management of Helicobacter pylori infection - the Maastricht IV/ Florence Consensus Report, Gut 2012;61:646-664; O'Connor A. et al. Treatment of Helicobacter pylori Infection 2015, Helicobacter 20 (S1) 54-61; Venerito M. et al. Meta-analysis of bismuth quadruple therapy versus clarithromycin triple therapy for empiric primary treatment of Helicobacter pylori infection. Digestion 2013;88(1):33-45. [13] Full prescribing information for Movantik® (naloxegol) is available at: . [14] Full prescribing information for Talicia® (omeprazole magnesium, amoxicillin and rifabutin) is available at: . [15] Full prescribing information for Aemcolo® (rifamycin) is available at: . Company Codes: NASDAQ-SMALL:RDHL, OTC-PINK:REDIF