Arterial Occlusive Diseases

MELBOURNE, Australia, April 7, 2024 /PRNewswire/ -- Cynata Therapeutics Limited (ASX: " CYP", "Cynata", or the "Company"), a clinical-stage biotechnology company specialising in cell therapeutics, is pleased to announce the completion of patient enrolment in its Phase 1 clinical trial of CYP-006TK in diabetic foot ulcers (DFU). CYP-006TK is Cynata's Cymerus™ iPSC[1]-derived MSC[2] topical wound dressing product candidate, which comprises MSCs seeded onto a novel silicon dressing. Due to reduced blood flow, patients with diabetes are at risk of developing non-healing wounds on the feet/lower limbs, which are also known as DFU. In addition to causing severe pain and discomfort, DFU pose a significant risk of infection, and if therapy is unsuccessful, amputation may be necessary. In this trial, CYP-006TK is being investigated as a potential treatment to promote wound healing in patients with DFU. The pre-specified sample size has now been reached, with a total of 30 patients with DFU randomised on a 1:1 basis to receive either: (i) CYP‑006TK treatment for four weeks, followed by standard of care treatment for the rest of the study; or (ii) standard of care treatment throughout the study. In accordance with the study protocol, patients will be followed for 24 weeks following treatment initiation, which means that the last patient visit in this trial is expected to occur around September 2024. Dr Jolanta Airey MD, Cynata's Chief Medical Officer, said: "We are delighted to have completed enrolment, and we extend our thanks to all of the investigators, study staff and patients for helping us to achieve this milestone. We recently announced very encouraging initial data from the first 16 patients enrolled in this trial after 10 weeks' follow-up, with a median percentage reduction in wound surface area of 87.6% in the active CYP-006TK group, compared to 51.1% in the control group. We now look forward to completing the follow-up period and releasing the full results from this study shortly thereafter." -ENDS- Authorised for release by Dr Kilian Kelly, CEO & Managing Director About Cynata Therapeutics (ASX: CYP) Cynata Therapeutics Limited (ASX: CYP) is an Australian clinical-stage stem cell and regenerative medicine company focused on the development of therapies based on Cymerus™, a proprietary therapeutic stem cell platform technology. Cymerus™ overcomes the challenges of other production methods by using induced pluripotent stem cells (iPSCs) and a precursor cell known as mesenchymoangioblast (MCA) to achieve economic manufacture of cell therapy products, including mesenchymal stem cells (MSCs), at commercial scale without the limitation of multiple donors. Cynata's lead product candidate CYP-001 met all clinical endpoints and demonstrated positive safety and efficacy data for the treatment of steroid-resistant acute graft-versus-host disease (GvHD) in a Phase 1 trial. A Phase 2 clinical trial in GvHD under a cleared US FDA IND, as well as trials of Cymerus products in osteoarthritis (Phase 3) and diabetic foot ulcers (DFU) are currently ongoing, while a trial in renal transplant is expected to commence in the near future. In addition, Cynata has also demonstrated utility of its Cymerus technology in preclinical models of numerous diseases, including critical limb ischaemia, idiopathic pulmonary fibrosis, asthma, heart attack, sepsis, acute respiratory distress syndrome (ARDS) and cytokine release syndrome. Cynata Therapeutics encourages all current investors to go paperless by registering their details with the designated registry service provider, Automic Group. [1] iPSC = induced pluripotent stem cell [2] MSC = mesenchymal stem (or stromal) cell SOURCE Cynata Therapeutics

Despite prevalence of chronic conditions associated with aortic stenosis in women over 65, the majority have never been referred to a cardiologist; Racial disparities may present further opportunities for awareness amongst women at risk for cardiovascular disease DUBLIN, April 7, 2024 /PRNewswire/ -- Medtronic plc, a global leader in healthcare technology, today unveiled topline findings of its comprehensive survey on women's perceptions and knowledge of risk factors, treatment patterns, and preventive care practices related to heart valve disease. The survey is endorsed by Women as One and was conducted by Wakefield Research sampling 1,000 women in the United States (U.S.) aged 50 and older. "In order to tackle the ever-growing challenges that female patients face in health care, we need to fully understand issues surrounding their awareness and the impact it has on their health," said Nina Goodheart, senior vice president and president, Structural Heart & Aortic, which is part of the Cardiovascular Portfolio at Medtronic. "Heart valve disease awareness deserves broader attention in the U.S., especially considering many women aged 50 and older are at an increased risk of developing the disease. This survey shines a light on the need for increased awareness, early detection, and access to appropriate care for women." The survey targeted a diverse sample of women aged 50 and above, with 53% between 50 to 65 years old and 47% aged 66 or older. Notably, 23.5% of respondents were Black or Hispanic, ensuring a nationally representative demographic of U.S. women in this age group. Findings from the survey highlight: There is a lack of awareness among women about the risks of aortic stenosis (AS) and cardiovascular disease. Despite the prevalence of cardiovascular disease amongst women, awareness is low, with 26% of women not having heard of any of the most common heart-related conditions such as coronary artery disease, congenital heart disease, heart valve disease, or AS, and only 30% of women aged 50 and older having heard of AS. Additionally, women of color have less awareness compared to their white counterparts, with only 10% of Black women and 21% of Hispanic women having heard of AS, compared to 33% of white women. Women are not referred for diagnosis and treatment. Even in women who present with risk factors, they are not always referred or screened- highlighting the opportunity to strengthen the referral and preventive screening pathway. In fact, 82% of women above age 65 are living with a chronic condition that increases their risk of aortic stenosis, yet the majority (68%) have never been referred to a cardiologist or taken a heart disease risk assessment. Women do not seek cardiovascular care because they believe their symptoms will not be taken seriously. Women experiencing heart valve disease symptoms such as fatigue and shortness of breath stated the following would prevent them for seeking medical care: More than 2 in five women cite fear or anxiety about going to the doctor 15% cite feeling like their doctor will dismiss their symptoms Women are interested in treatments that have been proven effective in women. For women diagnosed with a medical condition such as heart valve disease and deciding which treatment to pursue, they look to what would work best for them based on several important factors, such as minimally invasive treatment, recovery time, and doctor recommendation. When selecting the top three factors they consider, close to half (45%) include a minimally invasive procedure - highlighting the importance of solutions like TAVR. Additionally, the majority (75%) of women surveyed are very or extremely likely to ask their doctor about a different treatment option if they learn of one that is shown to be more effective in women than the one their doctor recommended. "When compared to male patients, female patients often present with more advanced symptoms of heart valve disease highlighting the importance of uncovering how we can best educate women on early warning signs and treatment options sooner," stated Roxana Mehran, MD, co-founder and president of Women as One. "These survey findings grant us the opportunity to develop better partnerships with communities experiencing the most inequities and provide a pathway to refining policies and systems that will lead to better care." Medtronic, Women as One, and others are spearheading a range of initiatives, from educational campaigns and women-focused clinical trial research with policymakers and government officials to increase health equity for women with heart valve disease. "Driving change to address inequities in healthcare cannot be done alone. When it comes to heart valve disease in women, Medtronic is proud to partner with our clinical community and organizations like Women as One to identify opportunities to improve health equity outcomes," added Goodheart. "Today at the American College of Cardiology Scientific Session, we look forward to further demonstrating this commitment with the results of our SMART trial, our latest effort to address the underrepresentation of women in cardiovascular health research." About Women and Aortic Stenosis Aortic stenosis (AS), a narrowing of the aortic valve, is among the most common of all valvular heart diseases, impacting 1.5 million in the U.S.1 Symptomatic severe aortic stenosis (ssAS) can be fatal if left untreated and the average patient survival is two years without treatment.2 Despite women's longer life expectancy, once impacted by ssAS, women suffer from higher mortality than men, even after matching for age.3 Alarmingly, 77% of women are living with chronic conditions that increase their risk of aortic stenosis, including high blood pressure (53%), high cholesterol (39%), and obesity (38%). Learn more at MyInteractiveASJourney.com. About Women as One Women as One is a 501(c)3 nonprofit organization, founded in 2019 by internationally recognized cardiovascular clinical trialists, Dr. Roxana Mehran and Dr. Marie-Claude Morice. The mission of the organization is to promote talent in medicine by providing unique professional opportunities to women cardiologists, knowing that diversity of thought and experience improves scientific discovery and patient outcomes. The organization provides programs and services ranging from clinical education and mentorship to clinical trial services. Through resources dedicated exclusively to women cardiologists and the patients they serve, Women as One effectively speeds up the rate at which gender disparities in cardiology are adequately addressed. About Medtronic Bold thinking. Bolder actions. We are Medtronic. Medtronic plc, headquartered in Dublin, Ireland, is the leading global healthcare technology company that boldly attacks the most challenging health problems facing humanity by searching out and finding solutions. Our Mission — to alleviate pain, restore health, and extend life — unites a global team of 95,000+ passionate people across 150 countries. Our technologies and therapies treat 70 health conditions and include cardiac devices, surgical robotics, insulin pumps, surgical tools, patient monitoring systems, and more. Powered by our diverse knowledge, insatiable curiosity, and desire to help all those who need it, we deliver innovative technologies that transform the lives of two people every second, every hour, every day. Expect more from us as we empower insight-driven care, experiences that put people first, and better outcomes for our world. In everything we do, we are engineering the extraordinary. For more information on Medtronic (NYSE: MDT), visit , and follow Medtronic on LinkedIn. Any forward-looking statements are subject to risks and uncertainties such as those described in Medtronic's periodic reports on file with the Securities and Exchange Commission. Actual results may differ materially from anticipated results. 1 Carabello BA, Paulus WJ. Aortic stenosis. Lancet. March 14, 2009;373(9667):956-966. 2 Lester SJ, Heilbron B, Gin K, Dodek A, Jue J. The natural history and rate of progression of aortic stenosis. Chest. April 1998;113(4):1109-1114. 3 Am Heart Assoc. 2021;10:e018816. DOI: 10.1161/JAHA.120.018816. Contact: Ryan Weispfenning Investor Relations +1-763-505-4626 Kimberly Powell Public Relations +1-202-498-2601 SOURCE Medtronic plc

V-INITIATE trial demonstrates that early initiation with Leqvio, prior to guideline-recommended ezetimibe, for ASCVD patients unable to achieve LDL-C goal on statin therapy alone led to significant LDL-C reduction vs. clinician-determined usual care (60% vs. 7% respectively)1 A significantly greater proportion of the ASCVD patients receiving Leqvio achieved guideline-recommended LDL-C goal vs. the usual care arm while maintaining adherence to statin treatment1 Results from usual care arm reinforce the urgent need for more aggressive LDL-C lowering in ASCVD patients, 92% of whom did not reach their LDL-C goal with statins alone1 The Leqvio safety profile was consistent with the Phase III clinical studies and long-term open-label extension trials for up to 6 years of treatment1-4 EAST HANOVER, N.J., April 6, 2024 /PRNewswire/ -- Novartis today announced new data demonstrating the early addition of twice-yearly* Leqvio® (inclisiran) to maximally tolerated statin therapy, prior to guideline-recommended ezetimibe, in a real-world setting significantly reduced low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD), including those with a history of an ASCVD-related event, who could not reach their goal on statin therapy alone1. The late-breaking data were presented at the 2024 American College of Cardiology's Annual Scientific Session & Expo and simultaneously published in the Journal of the American College of Cardiology. "V-INITIATE evaluated a solution to the important challenge seen in clinical practice of too many patients with ASCVD not achieving guideline-recommended LDL-C goal on statins alone and effective non-statin therapies being markedly underutilized," said Michael Koren, M.D., Medical Director and CEO of Jacksonville Center for Clinical Research, and the primary investigator of the study. "Given the urgent need to more aggressively manage LDL-C, the results from V-INITIATE show that when added earlier in the treatment continuum, the structured use of effective non-statin therapies like Leqvio can significantly reduce LDL-C for ASCVD patients who are struggling to reach or maintain their LDL-C goal." In the V-INITIATE study, patients receiving Leqvio experienced significant reductions in LDL-C compared to those receiving usual care (60% vs. 7%, respectively; p<0.001), which consisted mostly of statin therapy alone (73%)1. Four in five patients receiving Leqvio achieved the guideline-recommended LDL-C goal of <70 mg/dL compared to just one in five patients receiving usual care (81.8% vs. 22.2%, respectively; p<0.001)1. Notably, patients receiving health care provider (HCP)-administered Leqvio maintained adherence to existing lipid-lowering therapy, and the discontinuation rate of background statin therapy did not differ between the Leqvio and usual care arms (5.8% vs. 16.7%, respectively)1. The safety results from V-INITIATE were consistent with findings from the pivotal Phase III clinical trial program and long-term open-label extension trials, ORION-3 and ORION-8, which demonstrated sustained safety for up to six years of treatment1-4. "The data from V-INITIATE illustrate that earlier initiation of innovative non-statin therapies, like Leqvio, presents a real opportunity to do better for ASCVD patients and improve the way we approach LDL-C lowering," said David Soergel, M.D., Global Head of Cardiovascular, Renal and Metabolic Drug Development at Novartis. "This study adds data from a real-world setting to the growing body of evidence for Leqvio being generated through our robust VictORION program, and further reinforces the clinical value of this twice-yearly HCP-administered therapy." V-INITIATE is a 12-month Phase IIIb open-label study evaluating the effectiveness of adding Leqvio earlier, following a patient's failure to reach LDL-C goal on maximally tolerated statin therapy, compared to usual care, in a setting that reflects U.S. clinical practice. It was designed to more accurately represent the diversity of the U.S. general population across age, sex, race, ethnicity, insurance status, income level, education, prior medical history and statin intolerance1. Unlike placebo arms in typical double-blind trials, the usual care arm reflected U.S. clinical practice by allowing treating physicians to make changes to lipid-lowering treatment based on LDL-C measurements. Usual care was defined as clinician determined based on the 2018 American College of Cardiology/American Heart Association guideline recommendations1. *After an initial dose and another at three months. Indication LEQVIO (inclisiran) is an injectable prescription medicine used along with diet and other cholesterol-lowering medicines in adults with high blood cholesterol levels called primary hyperlipidemia (including a type of high cholesterol called heterozygous familial hypercholesterolemia [HeFH]) to reduce low-density lipoprotein (LDL-C) or "bad" cholesterol. Important Safety Information: The most common side effects of Leqvio were: injection site reaction (including pain, redness, and rash), arthralgia (joint pain), bronchitis (chest cold). These are not all the possible side effects of Leqvio. Ask your health care provider for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. Please click here for Leqvio full Prescribing Information. About Leqvio Leqvio is a subcutaneous injection given by a health care provider (HCP) with an initial dose, another at three months, and then every six months2,5. As a twice-yearly, HCP-administered treatment, Leqvio may help to circumvent the challenges of treatment adherence, a common issue in cholesterol management. Leqvio is the first and only small interfering RNA (siRNA) therapy to lower LDL-C. It is approved in over 90 countries, including the U.S., EU, Japan and China1,5,6. Novartis has obtained global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals, a leader in RNAi therapeutics. About V-INITIATE V-INITIATE is a 12-month, randomized, multicenter, open-label Phase IIIb study in 450 atherosclerotic cardiovascular disease (ASCVD) patients in the U.S. with elevated LDL cholesterol (LDL-C) ≥70 mg/dL. The study evaluated the effectiveness of adding HCP-administered Leqvio earlier, following a patient's failure to reach LDL-C goal on maximally tolerated statin therapy, compared to usual care1. Usual care was determined by the clinicians and based on the 2018 American College of Cardiology/American Heart Association guideline recommendations; most patients (73%) in the usual care arm remained on statins only1. The co-primary endpoints were the percentage change in LDL-C from baseline to Day 330 and the discontinuation of statin therapy, defined as no statin use ≥30 days before the end of study visit1. This is the first Novartis trial where all patients have been tokenized with the intention of following their outcomes for two additional years post-trial completion, providing additional insights on the real-world effectiveness of Leqvio7. About VictORION The V-INITIATE trial is part of VictORION, an innovative and robust clinical program for Leqvio, comprising more than 30 trials and enrolling over 60,000 patients in more than 50 countries worldwide7. The program is designed to expand on the foundational evidence of LDL-C reduction with Leqvio in diverse patient populations to include randomized clinical trials, implementation research, real-world evidence, and trials that aim to establish its potential benefits on cardiovascular outcomes in primary and secondary prevention. A growing number of studies are planned to generate a vast array of data with major trials such as ORION-4 (secondary prevention), V(VictORION)-2-PREVENT (secondary prevention), V-1-PREVENT (high-risk primary prevention), V-INCEPTION and V-MONO. About Atherosclerotic Cardiovascular Disease (ASCVD) ASCVD refers to a variety of diseases caused by the development and growth of plaques in the inner lining of the arteries8. The atherosclerotic plaque is mainly composed of low-density lipoprotein cholesterol (LDL-C) which accumulates over time8. Cumulative exposure to LDL-C is proportionally related to arterial plaque growth and progression leads to subsequent risk of cardiovascular events such as a heart attack or stroke8,9. Accounting for 85% of all cardiovascular disease deaths, ASCVD is the primary cause of mortality in the European Union and its burden in the United States is greater than that of any other chronic diseases10-13. ASCVD risk-equivalent corresponds to conditions that confer a similar risk for an ASCVD event (e.g., diabetes and heterozygous familial hypercholesterolemia)4,13. About Novartis in Cardiovascular Cardiovascular disease (CVD) affects hundreds of millions of people and claims more lives globally than cancer, chronic lung disease and diabetes combined14. It is time to change that. Around 80% of premature cardiovascular deaths can be prevented by addressing factors that cause or worsen CVD15. We have a responsibility to make that a reality for more people. Novartis has been advancing the scientific understanding and treatment of CVD for more than four decades. Through early intervention, pioneering science and technological innovation, we are addressing factors that increase the risk of heart attacks and strokes, improving the function of damaged hearts and easing the burden of care for patients. We also collaborate with healthcare professionals, patient communities and diverse organizations to improve preventive CV care worldwide. Together, we will help more people with CVD get the right treatments at the right time and live longer and healthier lives. Disclaimer This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "may," "could," "would," "expect," "anticipate," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people's lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. Reimagine medicine with us: Visit us at and and connect with us on LinkedIn, LinkedIn US, Facebook, X/Twitter, X/Twitter US and Instagram. Novartis previously filed its 2023 annual report with the Swiss SIX exchange in Switzerland, as well as its 2023 Annual Report on Form 20-F with the US Securities and Exchange Commission, and posted these documents on . Novartis shareholders may receive a hard copy of either of these documents, each of which contains our complete audited financial statements, free of charge, upon request. References Koren MJ, Rodriguez F, East CA, et al. Comparison of an "inclisiran first" strategy with usual care in patients with atherosclerotic cardiovascular disease: results from the VICTORION-INITIATE randomized trial. Data presented at: American College of Cardiology Congress; April 6, 2024; Atlanta, GA. Leqvio. Prescribing information. Novartis Pharmaceuticals Corp. Wright RS, Raal FJ, Koenig W, et al. ORION-8: Long-term efficacy and safety of twice-yearly inclisiran in high cardiovascular risk patients. Data presented at: European Society of Cardiology Congress; August 28, 2023; Amsterdam, the Netherlands. Ray KK, Troquay RPT, Visseren FLJ, et al. Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial. Lancet Diabetes Endocrinol. 2023;11(2):109-119. European Medicines Agency. Leqvio (inclisiran): An overview of Leqvio and why it is authorized in the EU. Last updated June 2021. Accessed March 12, 2024. National Medical Products Administration. Drug approval document delivery information. Published August 24, 2023. Accessed March 12, 2024. Data on file. NCT04929249. Novartis Pharmaceuticals Corp; 2024. Goldstein JL, Brown MS. A century of cholesterol and coronaries: from plaques to genes to statins. Cell. 2015;161(1):161-172. Ference BA, Graham I, Tokgozoglu L, Catapano AL. Impact of lipids on cardiovascular health: JACC Health Promotion Series. J Am Coll Cardiol. 2018;72(10):1141-1156. World Health Organization. Cardiovascular diseases (CVDs). Published June 11, 2021. Accessed March 12, 2024. (cvds) Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2-e220. Kim H, Kim S, Han S, et al. Prevalence and incidence of atherosclerotic cardiovascular disease and its risk factors in Korea: a nationwide population-based study. BMC Public Health. 2019;19(1):1112. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082–e1143. American Heart Association. More than half of U.S. adults don't know heart disease is leading cause of death, despite 100-year reign. Published January 24, 2024. Accessed March 12, 2024. World Heart Federation. World Heart Report. Published May 20, 2023. Accessed March 12, 2024. # # # SOURCE Novartis Pharmaceuticals Corporation