Gastrointestinal motility disorder

U.S.-based Professor Quigley brings decades of experience in gastroenterological clinical practice and research as a key opinion leader at the highest levels. Melbourne, Sydney, San Diego - May 1, 2023 Atmo Biosciences, a company commercializing the world’s first ingestible gas-sensing capsule that provides insights into gut health and microbiome function, today announced the appointment of renowned gastroenterologist Professor Eamonn Quigley as Chair of its Medical Advisory Board (MAB). Prof. Quigley is David M. Underwood Chair of Medicine in Digestive Disorders and Chief of Gastroenterology and Hepatology at Houston Methodist Hospital in Texas. He is internationally known for his research on gastrointestinal motility disorders, particularly irritable bowel syndrome (IBS) and its link to the gut microbiome. As Atmo MAB Chair, Prof. Quigley will provide leadership and guidance regarding Atmo’s clinical trials portfolio. “I am thrilled to have someone of Professor Quigley’s standing join our MAB as Chair,” said Atmo Biosciences CEO Malcolm Hebblewhite. “Eamonn is an internationally respected leader in gastroenterology. His ongoing research and thought leadership in the areas of motility and Small Intestinal Bacterial Overgrowth (SIBO) will be invaluable as we seek to develop these two key areas of focus in the U.S. and beyond.” Prof. Quigley of the appointment: “I am always excited by the promise of novel technologies that explore the gut microenvironment and the interactions between diet and the microbiome in particular. Atmo’s technology has the potential to serve as a valuable tool in both gastroenterological research and clinical practice. I am looking forward to sharing my insights with the other members of the Board and with Atmo.” Professor Quigley succeeds Professor Peter Gibson. Mr. Hebblewhite commented: “I want to thank Professor Gibson for the considerable contributions he has made to Atmo’s clinical development and the MAB to date. While he is stepping down as Chair, Peter will continue to play an active role with Atmo and the MAB, and I look forward to his ongoing involvement.” About Professor Eamonn M Quigley, MD, FRCP, FACP, MACG, FRCPI Prof. Quigley is David M. Underwood Chair of Medicine in Digestive Disorders, Chief of the Division of Gastroenterology and Hepatology, Medical Director of the Lynda K and David M Underwood Center for Digestive Disorders, and Professor of Medicine, Weill Cornell Medical College at Houston Methodist Hospital, Texas. He is also an Adjunct Professor of Medicine at Texas A and M University. Prior to joining Houston Methodist in 2013, Prof. Quigley was Dean of the Medical School at University College Cork and a principal investigator at the Alimentary Pharmabiotic Center (now Institute). He previously was Professor of Medicine and Chief of Gastroenterology and Hepatology at Nebraska Medical Center in Omaha, Nebraska. He has served as president of both the American College of Gastroenterology and the World Gastroenterology Organization and is a past editor-in-chief of the American Journal of Gastroenterology. He has authored over 1000 publications, mostly in the areas of gut motility, functional gastrointestinal disorders, and gastroesophageal reflux disease (GERD). About Atmo Biosciences: Atmo Biosciences is an Australian digital health business commercializing the world’s first ingestible, gas-sensing capsule which provides insight into gut health and microbiome function. Atmo’s gas-sensing capsule continuously measures clinically important gaseous biomarkers as it travels through the gut. Atmo aims to improve the diagnosis of common functional gut disorders, leading to more personalized treatments and earlier relief of symptoms for sufferers. The gas-sensing capsule is currently being used in research applications in multiple clinical trials around the world. Media Contacts: Atmo Biosciences Contact: Suraya Saleh and Mal Hebblewhite Telephone: +61 3 8803 4649 Email: suraya.saleh@atmobiosciences.com.au

Real-world analysis from the REVOLUTIONIZE I study showed hyperkalemia was recurrent following dietary counselling WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca will showcase five real-world evidence (RWE) studies from its industry-leading Cardiovascular, Renal and Metabolism (CVRM) portfolio, reinforcing its commitment to advancing science in chronic kidney disease (CKD) and hyperkalemia (HK), at the National Kidney Foundation (NKF) Spring Clinical Meeting April 11-15, 2023. AstraZeneca will present data from the REVOLUTIONIZE I RWE study that show the recurrent nature of HK in patients with CKD and demonstrate the unmet need for these patients.1 Sarah Walters, Vice President, US Cardiovascular, Renal & Metabolic Diseases, AstraZeneca, said, “We are dedicated to advancing clinically effective therapies to better support patients living with chronic kidney disease and hyperkalemia. Our data at the NKF Spring Clinical Meeting demonstrate our commitment to science and the potential role our approved medicines may play in improving patient lives.” Recurrence of HK following Medical Nutrition Therapy REVOLUTIONIZE I was a retrospective, observational, RWE study of US electronic health records that evaluated the recurrence of HK following a medical nutrition therapy (MNT) visit, also referred to as dietary counselling, in 2,048 adults with HK and Stage 3 or 4 CKD. Patients were followed up for 6 months post-MNT and were censored when they died or initiated outpatient potassium binder therapy. The study found that the percentage of patients with CKD Stage 3/4 who had recurrent HK increased from 1 month (37.4%) to 6 months (56%). When looking at the patient population from first HK recurrence (n=842) to the fourth HK recurrence (n=204), the average time between recurrences progressively decreased to less than 30 days over time (from 45 days to 27 days) and the percentage of patients with HK recurrence increased in those with a prior recurrence (from 56% to 70%) during the 6-month follow up post-MNT.1 The RWE study highlights the unmet need to consider adding an oral anti-HK therapy like LOKELMA for treating patients with HK.1 The REVOLUTIONIZE RWE is part of the CRYSTALIZE evidence program, which is comprised of over 50 clinical and RWE studies researching the potential role of LOKELMA in the management of HK across the cardiorenal spectrum. A comprehensive list of AstraZeneca key abstracts to be presented at the NKF Spring Clinical Meeting 2023 include: Lead author Abstract title Presentation details FARXIGA Dwyer J Short-Term Cost Impact of Dapagliflozin in Chronic Kidney Disease Poster #: 213 Hyperkalemia / LOKELMA Rowan C Recurrence of Hyperkalemia Following Dietary Counselling: REVOLUTIONIZE I Real-World Evidence Study Poster #: 296 Agiro A RAASi Optimization Among Patients Initiating SZC, OPTIMIZE I Real-World Evidence Study Poster #: 282 Dwyer J Impact of Sodium Zirconium Cyclosilicate Plus Renin-Angiotensin-Aldosterone System Inhibitor Therapy on Short-Term Medical Costs in Hyperkalemia: OPTIMIZE II study Poster #: 284 Dwyer J Medical Costs in Patients with Hyperkalemia on Long-Term Sodium Zirconium Cyclosilicate Therapy: RECOGNIZE II Study Poster #: 285 NKF Spring Clinical Meeting 2023 abstracts are available online. INDICATION AND LIMITATION OF USE FOR LOKELMA® (sodium zirconium cyclosilicate) 5 g and 10 g for oral suspension LOKELMA is indicated for the treatment of hyperkalemia in adults. LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS: Gastrointestinal Adverse Events in Patients with Motility Disorders: Avoid LOKELMA in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders. LOKELMA has not been studied in patients with these conditions and it may be ineffective and may worsen gastrointestinal conditions Edema: Each 5-g dose of LOKELMA contains approximately 400 mg of sodium, but the extent of absorption by the patient is unknown. In clinical trials of LOKELMA in patients who were not on dialysis, edema was observed and was generally mild to moderate in severity and was more commonly seen in patients treated with 15 g once daily. Monitor for signs of edema, particularly in patients who should restrict their sodium intake or are prone to fluid overload (eg, heart failure or renal disease). Advise patients to adjust dietary sodium, if appropriate. Increase the dose of diuretics as needed In a clinical trial of LOKELMA in patients on chronic hemodialysis in which most patients were treated with doses of 5 g to 10 g once daily on non-dialysis days, there was no difference in the mean change from baseline in interdialytic weight gain (a measure of fluid retention) between the LOKELMA and placebo groups Hypokalemia in Patients on Hemodialysis: Patients on hemodialysis may be prone to acute illness that can increase the risk of hypokalemia on LOKELMA (eg, illnesses associated with decreased oral intake, diarrhea). Consider adjusting LOKELMA dose based on potassium levels in these settings Diagnostic Tests: LOKELMA has radio-opaque properties and, therefore, may give the appearance typical of an imaging agent during abdominal X-ray procedures ADVERSE REACTIONS: The most common adverse reaction in non-dialysis patients with LOKELMA was mild to moderate edema. In placebo-controlled trials up to 28 days, edema was reported in 4.4%, 5.9%, 16.1% of non-dialysis patients treated with 5 g, 10 g, and 15 g of LOKELMA once daily, respectively vs 2.4% of non-dialysis patients receiving placebo. DRUG INTERACTIONS: LOKELMA can transiently increase gastric pH. In general, oral medications with pH-dependent solubility should be administered at least 2 hours before or 2 hours after LOKELMA. Spacing is not needed if it has been determined the concomitant medication does not exhibit pH-dependent solubility. PLEASE SEE US FULL PRESCRIBING INFORMATION FOR LOKELMA. INDICATIONS AND LIMITATIONS OF USE for FARXIGA® (dapagliflozin) FARXIGA is indicated: as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular (CV) disease or multiple CV risk factors to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction to reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression FARXIGA is not recommended for patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. FARXIGA is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m2. FARXIGA is likely to be ineffective in this setting based upon its mechanism of action. FARXIGA is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease. FARXIGA is not expected to be effective in these populations. DOSING To improve glycemic control, the recommended starting dose is 5 mg orally once daily. Dose can be increased to 10 mg orally once daily for additional glycemic control. For all other indications, the recommended dose is 10 mg orally once daily. IMPORTANT SAFETY INFORMATION for FARXIGA® (dapagliflozin) Contraindications Prior serious hypersensitivity reaction to FARXIGA Patients on dialysis Warnings and Precautions Ketoacidosis in Diabetes Mellitus has been reported in patients with type 1 and type 2 diabetes receiving FARXIGA. In placebo-controlled trials of patients with type 1 diabetes, the risk of ketoacidosis was increased in patients who received SGLT2 inhibitors compared to patients who received placebo. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue FARXIGA, evaluate and treat promptly. Before initiating FARXIGA, consider risk factors for ketoacidosis. Patients on FARXIGA may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis Volume Depletion: FARXIGA can cause intravascular volume depletion which may manifest as symptomatic hypotension or acute transient changes in creatinine. Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes receiving SGLT2 inhibitors, including FARXIGA. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating FARXIGA in these patients, assess volume status and renal function. After initiating therapy, monitor for signs and symptoms of hypotension and renal function Urosepsis and Pyelonephritis: SGLT2 inhibitors increase the risk for urinary tract infections (UTIs) and serious UTIs have been reported with FARXIGA. Evaluate for signs and symptoms of UTIs and treat promptly Hypoglycemia: FARXIGA can increase the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with FARXIGA Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Rare but serious, life-threatening cases have been reported in patients with diabetes mellitus receiving SGLT2 inhibitors including FARXIGA. Cases have been reported in females and males. Serious outcomes have included hospitalization, surgeries, and death. Assess patients presenting with pain or tenderness, erythema, swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment and discontinue FARXIGA Genital Mycotic Infections: FARXIGA increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately Adverse Reactions In a pool of 12 placebo-controlled studies, the most common adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and placebo respectively were female genital mycotic infections (8.4% vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract infections (5.7% vs 4.3% vs 3.7%). Use in Specific Populations Pregnancy: Advise females of potential risk to a fetus especially during the second and third trimesters Lactation: FARXIGA is not recommended when breastfeeding PLEASE SEE US Full Prescribing Information for FARXIGA. Notes AstraZeneca in CVRM Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s three disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection and improving outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company’s ambition is to modify or halt the natural course of CVRM diseases, and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide. About AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit and follow us on Twitter @AstraZenecaUS. References Rowan CG, et al. Recurrence of hyperkalemia following dietary counselling, REVOLUTIONIZE I Real-World Evidence Study. Presented at National Kidney Foundation (NKF) Spring Clinical Meetings (SCM) 2023, 22-25 April, 2023, Austin, Texas, USA. US-74793 Last Updated 4/23

Engineers at MIT and Caltech have developed an ingestible sensor that could more easily diagnose gastrointestinal motility disorders. This advance could help with the diagnosis of constipation, gastroesophageal reflux disease and gastroparesis. The engineers designed their tiny sensor to detect a magnetic field produced by an electromagnetic coil located outside of the patient’s body. The strength of the field varies with distance from the coil, which allows for the calculation of the sensor’s position based on its measurement of the magnetic field. In a new study, the researchers demonstrated the ability to track the sensor as it moved through the digestive tract of large animals. They believe this could offer an alternative to more invasive procedures — like endoscopy — used to diagnose motility disorders. Giovanni Traverso, associate professor of mechanical engineering at MIT, is one of the senior authors of the study, published today in Nature Electronics. Traverso also works as a gastroenterologist at Brigham and Women’s Hospital. “Many people around the world suffer from GI dysmotility or poor motility, and having the ability to monitor GI motility without having to go into a hospital is important to really understand what is happening to a patient,” said Traverso. Azita Emami, a professor of electrical engineering and medical engineering at Caltech, and Mikhail Shapiro, a professor of chemical engineering at Caltech and an investigator of the Howard Hughes Medical Institute, were senior authors. Saransh Sharma, a Caltech grad student, and Khalil Ramadi, assistant professor of bioengineering at New York University, were lead authors. How the sensor works The engineers said they wanted to come up with a less invasive alternative to endoscopy that can be done at the patient’s home. Related: Endiatx’s pill-sized robot sees and swims inside the stomach The researchers developed a sensor small enough to fit inside an ingestible capsule to take advantage of the distance factor and its effect on the strength of the electromagnetic coil. The sensor measures the surrounding magnetic field to calculate its distance from the coil outside the body. “Because the magnetic field gradient uniquely encodes the spatial positions, these small devices can be designed in a way that they can sense the magnetic field at their respective locations,” Sharma said. “After the device measures the field, we can back-calculate what the location of the device is.” The system also includes a second sensor that remains outside the body — taped to the skin, for example — to act as a reference point. It allows the researchers to accurately calculate where the sensor in the GI tract is located. The researchers said their ingestible sensor also includes a wireless transmitter. This transmitter sends the measurements to a nearby computer or smartphone. Currently, the researchers have a design that takes a measurement any time it receives a wireless trigger. However, they say they can program it to take measurements at specific intervals. At present, the sensor can detect a magnetic field from coils within a distance of 60 centimeters or less. The researchers say they could place coils in a patient’s backpack or jacket. This allows the ingestible sensor to take measurements whenever in range. More on the location tracking The researchers tested their system in a large animal model. They placed the capsule in the stomach and monitored its location as it moved through the digestive tract over several days. In the first attempt, the researchers delivered two magnetic sensors attached to each other by a small rod. That ensured they knew the exact distance between them. They compared measurements to the known distance and found they were accurate to about two millimeters. Then, the researchers tested a single ingestible sensor with an external sensor attached to the skin. They found that they could track it as it moved from the stomach to the colon before excretion. Comparing their accuracy with X-ray measurements, the researchers determined accuracy within five to 10 millimeters. “Using an external reference sensor helps to account for the problem that every time an animal or a human is beside the coils, there is a likelihood that they will not be in exactly the same position as they were the previous time,” Ramadi said. “In the absence of having X-rays as your ground truth, it’s difficult to map out exactly where this pill is, unless you have a consistent reference that is always in the same location.” The researchers aim to work with collaborators to develop manufacturing processes for the system. They believe this method could make it easier for doctors to determine where slowdowns occur in the GI tract. According to MIT, they hope to eventually bring it to human clinical trials. “The ability to characterize motility without the need for radiation, or more invasive placement of devices, I think will lower the barrier for people to be evaluated,” Traverso said. The National Science Foundation, the Rothenberg Innovation Initiative, and the Heritage Medical Research Institute funded the research. Related: 29 cutting-edge medtech innovations recognized with Edison Awards