Hypertension, Renal

KARDIA-2 study met its primary endpoint, demonstrating clinically significant systolic blood pressure reductions in each treatment arm at month three Zilebesiran added to a standard of care hypertension medication demonstrated an encouraging safety and tolerability profile in adults with mild to moderate uncontrolled hypertension, and results support the potential for twice-yearly dosing Roche and Alnylam have initiated the Phase II KARDIA-3 study in adults with uncontrolled hypertension at high cardiovascular riskKARDIA-2 study results will be presented as a late-breaking abstract in April at the 2024 American College of Cardiology Annual Scientific Session Basel, 05 March 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) and Alnylam announced today that the Phase II KARDIA-2 study [NCT05103332] of zilebesiran, an investigational RNAi therapeutic in development for the treatment of hypertension (high blood pressure) - the leading cause of cardiovascular disease worldwide1 - met its primary endpoint. People with mild to moderate hypertension treated with zilebesiran added to a standard of care hypertension medication experienced a clinically and statistically significant reduction in systolic blood pressure at month three. Zilebesiran added to a standard of care demonstrated an encouraging safety and tolerability profile. “With twice-yearly dosing in combination with standard of care medication, zilebesiran has strong potential to sustain lower blood pressure and reduce the risk of stroke, heart attack and death that can result from inadequate treatment,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We look forward to continuing the zilebesiran Phase II study programme with Alnylam as we seek to provide transformative impact for millions of people living with uncontrolled hypertension.’’ Hypertension, or high blood pressure, is the leading cause of cardiovascular disease worldwide and a major risk for premature mortality.1 It is a growing global health crisis, responsible for around 10 million deaths worldwide each year.2 Approximately one in three adults are living with hypertension globally, and there remains a significant unmet medical need given the poor rates of adherence to existing treatments.3 Currently, up to 80% of people with hypertension have blood pressure that remains uncontrolled despite the availability of several classes of oral hypertension treatments, leaving them at an increased risk of cardiovascular, cerebrovascular, and renal disease.4-8 The Phase II KARDIA-2 trial results will be presented as a late-breaking abstract at the 2024 American College of Cardiology Annual Scientific Session (6-8 April 2024, Atlanta, Georgia, USA). The KARDIA-2 results build on the positive Phase II KARDIA-1 [NCT04936035] data, presented at the congress of the American Heart Association Scientific Sessions in November 2023, and published in JAMA in February 2024.9,10 Roche and Alnylam have now initiated the global Phase II KARDIA-3 study [NCT06272487] designed to evaluate the efficacy of zilebesiran when added to two or more hypertension medications in people with uncontrolled hypertension at high cardiovascular risk. About the KARDIA-2 study11The Phase II KARDIA-2 trial is a randomised, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of zilebesiran, when added to a standard of care, in adults with mild-to-moderate hypertension. This global, multicentre trial enrolled 672 adults with hypertension. Patients who met all inclusion/exclusion criteria during a screening period were randomised into three different cohorts to receive open-label therapy with olmesartan, amlodipine or indapamide as their protocol-specified background hypertension medication during a run-in period of at least four weeks. Following the run-in period, eligible patients were randomised 1:1 to receive zilebesiran 600 mg or placebo in addition to their protocol-specified background hypertension medication for six months. The primary endpoint is the change from baseline mean systolic blood pressure (SBP) at month three, assessed by 24-hour ambulatory blood pressure monitoring (ABPM). Additional endpoints include the change in 24-hour mean SBP after six months of treatment assessed by ABPM, change in office SBP at months three and six, and change in diastolic blood pressure measured by ABPM and office blood pressure at months three and six. Safety will be assessed throughout the study. About zilebesiranZilebesiran is an investigational, subcutaneously administered RNAi therapeutic targeting angiotensinogen (AGT) in development for the treatment of hypertension in high unmet need populations. AGT is the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), a cascade which has a demonstrated role in blood pressure regulation and its inhibition has well-established antihypertensive effects. Zilebesiran inhibits the synthesis of AGT in the liver, potentially leading to durable reductions in AGT protein and ultimately, in the vasoconstrictor angiotensin (Ang) II. Zilebesiran utilises Alnylam's Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables infrequent subcutaneous dosing with increased selectivity and the potential to achieve tonic blood pressure control demonstrating consistent and durable blood pressure reduction throughout a 24-hour period, sustained up to six months after a single dose of zilebesiran. The safety and efficacy of zilebesiran have not been established or evaluated by the U.S. Food and Drug Administration, European Medicines Agency, or any other health authority. Zilebesiran is being co-developed and co-commercialised by Roche and Alynlam. Zilebesiran Phase II clinical development overview: Study Overview of protocol KARDIA-1 [NCT04936035] Evaluated zilebesiran monotherapy in people with mild to moderate hypertension. Met primary endpoint. KARDIA-2 [NCT05103332] Evaluated zilebesiran when added to a standard of care hypertension medication in people with mild to moderate hypertension. Met primary endpoint. KARDIA-3 [NCT06272487] Designed to evaluate zilebesiran when added to two or more hypertension medications in people with uncontrolled hypertension at high cardiovascular risk. About hypertension More than one billion adults are living with hypertension worldwide, which is a major risk factor for cardiovascular disease and premature mortality.4 Early effects of hypertension can include subtle target organ damage such as left-ventricular hypertrophy and cognitive dysfunction.12,13 Over time, uncontrolled hypertension can lead to cardiovascular disease including stroke (ischaemic and haemorrhagic), coronary artery disease, heart failure, peripheral artery disease, chronic kidney disease and end-stage renal disease, dementia, and Alzheimer’s disease.5-8There remains a significant unmet medical need, as poor rates of adherence to daily medications can result in inconsistent blood pressure control and an increased risk for stroke, heart attack, and premature death.3 In particular, there are a number of high unmet need settings where novel approaches to hypertension warrant additional development focus, including patients with high cardiovascular risk.14 About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the fifteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com. All trademarks used or mentioned in this release are protected by law.References[1] Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020;16:223-237. https://doi.org/10.1038/s41581-019-0244-2.[2] World Heart Federation. Hypertension [Internet; cited February 2024]. Available from: https://world-heart-federation.org/what-we-do/hypertension/#:~:text=It%20affects%20an%20estimated%201.3,10%20million%20people%20every%20year.[3] Burnier M, Egan BM. Adherence in Hypertension. Circ. Res. 2019;124:1124-1140. https://doi.org/10.1161/CIRCRESAHA.118.313220.[4] World Health Organization. Hypertension [Internet; cited February 2024]. Available from: https://www.who.int/news-room/fact-sheets/detail/hypertension.[5] Oparil S, et al. Hypertension. Nat Rev Dis Primers. 2018;4:18014. https://doi.org/10.1038/nrdp.2018.14.[6] Nazarzadeh M, et al. JAMA Cardiol. Systolic Blood Pressure and Risk of Valvular Heart Disease: A Mendelian Randomization Study. 2019;4(8):788-795.[7] Thorin E, Hypertension and Alzheimer Disease. J. Hypertens. 2015;65:36-38.[8] Mennuni S, et al. Hypertension and kidneys: unraveling complex molecular mechanisms underlying hypertensive renal damage. J Hum Hypertens. 2014;28:74-79. doi: 10.1038/jhh.2013.55.[9] Bakris GL, et al. Sustained Blood Pressure Reduction With the RNA Interference Therapeutic Zilebesiran: Primary Results From KARDIA-1, a Phase 2 Study in Patients With Hypertension. Presented at: American Heart Association Scientific Sessions; 2023 November 11-12; Philadelphia, Pennsylvania, USA. Abstract LBS.04.[10] Bakris GL, et al. RNA Interference With Zilebesiran for Mild to Moderate Hypertension: The KARDIA-1 Randomized Clinical Trial. JAMA. Published online, February 16, 2024. doi:10.1001/jama.2024.0728.[11] Clinicaltrials.gov. Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2) [Internet; cited February 2024]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05103332?term=Zilebesiran&draw=2. [12] Bruno A, et al. Left ventricular hypertrophy in acute stroke patients with known hypertension. Clin Exp Hypertens. 2017;39:502-504. doi:10.1080/10641963.2016.1259328.[13] Poon, IO. Effects of antihypertensive drug treatment on the risk of dementia and cognitive impairment. Pharmacotherapy. 2008;28:366-375. doi: 10.1592/phco.28.3.366.[14] World Health Organization. Cardiovascular Death and Disability can be reduced more than 50 percent [Internet; cited February 2024]. Available from: https://www.who.int/news/item/17-10-2002-cardiovascular-death-and-disability-can-be-reduced-more-than-50-percent. Roche Global Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 Nathalie AltermattPhone: +41 79 771 05 25 Simon GoldsboroughPhone: +44 797 32 72 915 Karsten KleinePhone: +41 79 461 86 83 Nina MählitzPhone: +41 79 327 54 74 Kirti PandeyPhone: +49 172 6367262 Dr. Rebekka SchnellPhone: +41 79 205 27 03 Sileia UrechPhone: +41 79 935 81 48 Roche Investor Relations Dr. Bruno Eschli Phone: +41 61 68-75284 e-mail: bruno.eschli@roche.com Dr. Sabine BorngräberPhone: +41 61 68-88027 e-mail: sabine.borngraeber@roche.com Dr. Birgit MasjostPhone: +41 61 68-84814e-mail: birgit.masjost@roche.com Investor Relations North America Loren KalmPhone: +1 650 225 3217 e-mail: kalm.loren@gene.com Attachment 05032024_MR_KARDIA-2 Roche_EN

SEATTLE, Feb. 28, 2023 (GLOBE NEWSWIRE) --Chinook Therapeutics, Inc. (Nasdaq: KDNY), a biopharmaceutical company focused on the discovery, development and commercialization of precision medicines for kidney diseases, today announced upcoming presentations at the 5th Chronic Kidney Disease Drug Development (CKD) Summit in Boston, MA from March 7 – 9, 2023. Chinook will participate in the following panel discussions and presentation: Panel Discussion: Rare, Diabetic & Hypertensive Kidney Disease: What do Payers and Regulators Need to See? Beyond hard endpoints: what is an approvable and achievable endpoint in diabetic and rare kidney diseases? Harmonizing global regulations and patient metrics Considering future principles of reimbursement and benchmarking clinical benefit in the context of new approved therapies Date/Time: Wednesday, March 8, 2023 at 3:00 pm EST Participant: Tom Frohlich, Chief Operating Officer of Chinook Therapeutics Presentation: From Positive Proof of Concept to Phase III Registration Trial: Designing & Executing Robust Clinical Trials in Rare Disease Indications Accelerating development of BION-1301 for the treatment of IgAN Exploring disease-modifying biomarkers assessments and optimizing trial design in rare disease populations To orphan drug designation and beyond: enhancing clinical outcome in defined patient cohorts Date/Time: Thursday, March 9, 2023 at 8:00 am EST Participant: Andrew King, DVM, PhD, Chief Scientific Officer of Chinook Therapeutics Panel Discussion: Accelerated Approval, Small Patient Populations & Precision Medicine: Executing Clinical Trials in Rare Kidney Diseases Clarifying heterogeneous disease pathogenesis to investigate exciting targets Analyzing the landscape for early and disease specific biomarkers to monitor disease progression Navigating patient enrollment in the context of exploding competition for patients with specific disease criteria Date/Time: Thursday, March 9, 2023 at 9:30 am EST Participant: Andrew King, DVM, PhD, Chief Scientific Officer of Chinook Therapeutics Panel Discussion: Redefining Inclusion & Exclusion Criteria in Trials to Optimize Development & Study Multiple Outcomes Navigating inclusion of patients with underlying conditions and comorbidities Diabetic complications, cardiovascular complications, children and transplant patients: who should we be including in trials? Rethinking patient selection through reviewing staging, fast progressors and comorbidities to reflect target patient groups Date/Time: Thursday, March 9, 2023 at 11:00 am EST Participant: Charlotte Jones-Burton, MD, MS, Senior Vice President of Product Development and Strategy of Chinook Therapeutics For more information on these and other presentations, please visit the CKD Summit website. About Chinook Therapeutics, Inc. Chinook Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing precision medicines for kidney diseases. Chinook’s product candidates are being investigated in rare, severe chronic kidney disorders with opportunities for well-defined clinical pathways. Chinook’s lead program is atrasentan, a phase 3 endothelin receptor antagonist for the treatment of IgA nephropathy and proteinuric glomerular diseases. BION-1301, an anti-APRIL monoclonal antibody, is being evaluated in a phase 1/2 trial for IgA nephropathy. CHK-336, an oral small molecule LDHA inhibitor for the treatment of hyperoxalurias, is being evaluated in a phase 1 clinical trial in healthy volunteers. In addition, Chinook’s research and discovery efforts are focused on building a pipeline of precision medicines for rare, severe chronic kidney diseases with defined genetic and molecular drivers. Chinook is leveraging insights from kidney single cell RNA sequencing and large CKD patient cohorts that have been comprehensively panomically phenotyped, with retained biosamples and prospective clinical follow-up, to discover and develop therapeutic candidates with mechanisms of action targeted against key kidney disease pathways. To learn more, visit . Cautionary Note on Forward-Looking Statements Certain of the statements made in this press release are forward looking, including those relating to Chinook’s business, future operations, advancement of its product candidates and product pipeline, clinical development of its product candidates, including expectations regarding cash forecasts and timing of initiation and results of clinical trials, and regulatory submissions, including the timing of the results of our phase 3 ALIGN trial and phase 2 AFFINITY trial of atrasentan, phase 1 clinical trial of CHK-336, and submission for potential accelerated approval. In some cases, you can identify these statements by forward-looking words such as “may,” “will,” “continue,” “anticipate,” “intend,” “could,” “project,” “expect” or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, including initiation of clinical trials of our existing product candidates or those developed as part of the Evotec collaboration or other strategic collaborations, whether results of early clinical trials or preclinical studies will be indicative of the results of future trials, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that may be more advanced or have greater resources than we do, our ability to obtain and adequately protect intellectual property rights for our product candidates, and the effects of COVID-19 and macroeconomic conditions on our clinical programs and business operations. Many of these risks are described in greater detail in our filings with the SEC. Any forward-looking statements in this press release speak only as of the date of this press release. Chinook assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. Contact: Noopur Liffick, MPH Senior Vice President, Investor Relations & Corporate Communications investors@chinooktx.com media@chinooktx.com

The company's growing number of solutions for structural heart disease will be presented at multiple events during the conference between November 27-29 HANGZHOU, China, Nov. 25, 2022 /PRNewswire/ -- Venus Medtech is building an exciting pipeline of treatments for structural heart disease. The company will present its products at the conference taking place at the ExCeL London November 27-29, 2022 in its booth (#25), during a symposium, and at the official launch of the TARGET multicenter clinical study. Structural heart symposium on November 27 The company will also be hosting a symposium on November 27 (Hall #4 at 17:30 pm) where top investigators will discuss the latest results and future plans for the Venus Medtech tricuspid and pulmonary valve replacement systems. During this symposium, "The Right Valves for The Right Ventricle: Venus MedTech tricuspid and pulmonary replacement systems," interventional cardiologists will have the opportunity to learn the latest about structural heart interventions. Launch of TARGET CE Study for tricuspid valve replacement on November 28 Additionally, Venus Medtech will be officially launching the TARGET study at the conference. The TARGET study will evaluate the safety and performance of the Cardiovalve Tricuspid System—with its associated procedure—in reducing tricuspid regurgitation and the associated symptoms. The Cardiovalve system includes a valve and delivery system, designed for replacement of the tricuspid valve through a transcatheter approach. The study will enroll one hundred patients in up to thirty medical centers. Patients will be followed for a period of up to five years. The TARGET CE Study will be launched officially at the Sunborn London Yacht Hotel on Monday, November 28 at 18:30 pm. Presentation of new data The experiences with Cardiovalve and presentation of new data will be held in the following sessions: Dr. Estevez-Loureiro, Eliminate tricuspid regurgitation: transfemoral CardioValve tricuspid replacement system (Tricuspid interventions session, November 27, 13:30 - 15:00 at Interactive Case Corner 2). Dr. Sherif, Transcatheter transseptal mitral valve implantation: a new tool-in-the-box for patients with severe mitral regurgitation (TMVR challenges session, November 27, 15:05 - 16:05, at Interactive Case Corner 2). Dr. Schmidt, Transcatheter valve implantation in mitral and tricuspid valve position, (Rapid-fire clinical cases: Session 7, November 29, 14:50 - 15:35 at The Exchange). About Venus Medtech: Increasing global presence Venus Medtech (stock code: 2500.HK) is committed to structural heart innovation. As the leading transcatheter heart valve medical device player in China, Venus Medtech has established comprehensive solutions for structural heart disease. It now has a complete product pipeline covering all four heart valves, namely TAVR, TPVR, TMVR and TTVR, as well as hypertrophic cardiomyopathy, hypertensive renal denervation (RDN) therapy and relevant accessory products. Venus is now intensifying its presence in overseas markets, making important breakthroughs in registration and commercialization. For more information Visit our conference website: SOURCE Venus Medtech (Hangzhou) Inc.