Edoxaban Tosylate

MUNICH--( BUSINESS WIRE )--Daiichi Sankyo Europe, (hereafter, Daiichi Sankyo) today announced its reinforced commitment to addressing key unmet needs and barriers in cardiovascular (CV) care, by shining a light on inequalities in treatment and outcomes experienced by various patient groups. The announcement follows the presentation of data from sub-analyses of the SANTORINI observational study and ETNA-AF (Edoxaban Treatment in routiNe clinical prActice in patients with nonvalvular Atrial Fibrillation) study programme, at the European Society of Cardiology (ESC) Congress 2024. Gender inequalities in CV disease treatment and LDL-C goal attainment Raised low-density lipoprotein cholesterol (LDL-C) is a key modifiable contributor to risk of cardiovascular major events. It has been shown that for every 1 mmol/L reduction in LDL-C, there is a 22% reduction in major cardiovascular events after 1 year. 7,8 Female patients in Europe who are at high or very high CV risk were undertreated and less achieved guideline-recommended LDL-C levels, according to data from the observational SANTORINI study. 1 As part of its efforts to expand medical knowledge to help protect people from CV disease (CVD), Daiichi Sankyo funds and designs studies, such as SANTORINI, that investigate the underlying causes behind the burden of CVD in Europe. Data from a new sub-analysis of SANTORINI, based on 5,197 male patients with a mean age of 65 years, and 2,013 females with a mean age of 66 years, showed that female patients were undertreated compared to men as fewer achieved guideline-recommended LDL-C levels within the study. 1 While the proportion of patients reaching LDL-C goals improved from baseline to 1-year follow up, it was greater in males (22.9% and 33.3%, respectively) than in females (16.9% and 24.6%,). 1 Despite similar guideline recommendations, more females received no lipid-lowering therapies at baseline and 1-year follow up (23.9% to 3.9%, respectively) than males (20.7% to 2.7%). 1 “We know that the severity of cardiovascular disease for women is as high as it is with men, and patients of both sexes remain undertreated. 9,10 But this new sub-analysis of the SANTORINI study further suggests that in clinical practice, women as a group were being disproportionally undertreated and do not always reach recommended LDL-C level goals,” said Professor David Nanchen, University of Lausanne, Center for Primary Care and Public Health (Unisanté), Lausanne, Switzerland. “These findings underscore the need for more widespread attention to better manage the risk of cardiovascular disease in women. ” Treatment adherence and the impact of non-adherence on patient outcomes Treatment for atrial fibrillation with oral anticoagulation relies on adherence and persistence to be effective. Non-persistence to single non-vitamin K antagonist oral anticoagulants (NOACs) has been associated with increased stroke risk in atrial fibrillation (AF) patients. 2 Daiichi Sankyo committed to ETNA-AF, which combines data from distinct non-interventional studies in Europe, East Asia, and Japan in a single database, to delve deeper into the global burden of CVD. More than 28,000 patients were included in the ETNA-AF registries and followed for four years in Europe and two years in countries outside Europe. 11 Results from a new post hoc sub-analysis of the ETNA-AF programme showed that, of the 9,417 [13,164 enrolled] (71.5%) patients who completed the 4-year study, 87.4% were persistent with edoxaban treatment. 3 Treatment discontinuation and non-persistence were both associated with factors including increasing age, male sex, body weight extremes, low renal function, heart failure, vascular disease, chronic hepatic disease, alcohol use, perceived frailty, chronic obstructive pulmonary disease, smoking, current AF symptoms, and ablation. 3 “The high number of patients who persisted with edoxaban treatment for the duration of the 4-year study is good news for our efforts to mitigate therapeutic non-adherence, 2 ” said Professor Raffaele De Caterina, MD, PhD, FESC, Director of Cardiology at Pisa University Hospital. “ We hope that the associated factors for non-persistence observed in the study will also assist the development of treatment strategies in clinical practice, for the benefit of patient outcomes.” Treatment for patients with frailty and comorbidities Barriers to recommending anticoagulation to manage non-valvular AF (NVAF), such as complex multimorbidities are significant in frail patients. 12 As such, the prescription of NOACs in the frail patient population is <50%. 12 Doctors are required to balance stroke risk and bleeding risk when making prescribing decisions. 12 Frailty is a common reason to choose non recommended doses of NOACs and so the four year follow up data from ETNA-AF were used to assess clinical outcomes in such patients. Patients with 'perceived' or objective frailty who were treated with a reduced (non-recommended) 30mg dose showed a higher rate of all-cause death versus the 60mg dose (HR [95% CI]: 1.44[1.06,1.96]) with no significant effect on major bleeding. This suggests that the presence of frailty per se should not necessarily drive dose reductions. 5 In a separate sub analysis of the data, patients were divided into low, middle and high tertiles based on body mass index (BMI), body surface area (BSA) and lean body mass (LBM). Rates of thromboembolic events were low (0.7-0.9%/100PY) and similar across tertiles. However, higher rates of any haemorrhagic events were observed in the low ([2.2–2.4%]) vs middle ([1.5–1.8%]) and high ([1.4–1.5%]) tertiles for BSA and LBM, suggesting that these variables, more than BMI, should be considered when analysing outcomes in patients treated with edoxaban. 4,6 “At Daiichi Sankyo, we continue in our long-term commitment to provide scientific evidence that can support the optimal treatment of patients with cardiovascular disease, and to find solutions for individuals who have previously been undertreated,” said Dr. Stefan Seyfried, Vice President Medical Affairs, Specialty Medicines, at Daiichi Sankyo Europe GmbH. “ Our promise to patients is to continue shining a light on treatment inequalities and unmet needs in cardiovascular care, with the goal of reducing the burden on patients and their loved ones. ” -ENDS- About SANTORINI The SANTORINI study is a multinational, prospective, observational study that enrolled 9,602 patients with high and very high CV risk from over 623 sites in 14 countries across Europe. Patients were recruited between March 2020 and February 2021. 10 The primary objective was to document, in the real-world setting, the effectiveness of current LDL-C management approaches in high- and very high-cardiovascular-risk patients requiring lipid-lowering therapies over a 1-year period. 10 The study included both previously diagnosed and treated patients and those newly diagnosed and requiring treatment. 10 Complete baseline data was included for 9,044 patients (mean age: 65.3 ± 10.9 years; 72.6% male). 10 Physicians used 2019 ESC/EAS guidelines as a basis for CV risk classification in 52% of patients; 29.2% of patients were classified as high risk and 70.8% as very high risk. 10 Central reassessment with the same guidelines classified 6.5% as high risk and 91% as very high-risk. 10 Overall, 21.8% of patients had no documented lipid lowering therapies (LLTs), 54.2% were receiving monotherapy and 24% combination LLT. 10 Median LDL-C was 2.1 mmol/L with 20.1% of patients achieving risk-based LDL-C goals as per the 2019 ESC/EAS guidelines. 10 About ETNA-AF ETNA-AF (Edoxaban Treatment in routiNe clinical prActice in patients with nonvalvular Atrial Fibrillation) is a global programme that combines data from distinct non-interventional studies in Europe, East Asia, and Japan in a single database. A total of more than 28,000 patients were included in the ETNA-AF registries and followed for two years (patients in Europe were followed for four years). 11 The primary objective of ETNA-AF was to collect information on the use of edoxaban in routine clinical practice, including the safety and efficacy profile in non-preselected patients with nonvalvular AF. 13,14,15,16,17 About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops, and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular, and other diseases with high unmet medical need. For more information, please visit https://www.daiichi-sankyo.eu/ References ________________________________ 1 Nanchen, D., et al. Contemporary LDL-cholesterol management in male and female patients at high-cardiovascular risk: results from the European observational SANTORINI study. Oral presentation, ESC Congress 30 August 2024. 2 Vitolo, M., et al. The importance of adherence and persistence with oral anticoagulation treatment in patients with atrial fibrillation. European Heart Journal – Cardiovascular Pharmacotherapy. 2021. 7;(FI1): f81–f83 3 Diemberger, I., et al . Persistence and predictors for non-persistence to edoxaban therapy in patients with atrial fibrillation: 4-year follow-up data from the ETNA-AF-Europe study. ESC Congress 2024 4 Boriani, G., et al . Impact of differences in body mass index, body surface area and lean body mass on clinical outcomes in patients with atrial fibrillation receiving edoxaban: 4-year follow-up data from ETNA-AF-Europe. ESC 2024 5 Fumagalli, S., et al . Edoxaban dose, frailty, and outcomes in patients with atrial fibrillation: the ETNA-AF-Europe 4-year follow-up. ESC 2024 6 Boriani, G., et al . Impact of body weight and body mass index on clinical outcomes of edoxaban therapy in atrial fibrillation patients included in the ETNA-AF-Global registry. ESC 2024 7 Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 2010. 376(9753): 1670–1681 8 NHS England. Improving lipid management to reduce cardiovascular disease and save lives. Available at: https://www.england.nhs.uk/long-read/improving-lipid-management-to-reduce-cardiovascular-disease-and-save-lives/#:~:text=Raised%20LDL%20cholesterol%20is%20one,vascular%20events%20after%201%20year . Last accessed August 2024. 9 ESC. Cardiovascular Disease in Women. Available at: https://www.escardio.org/The-ESC/Advocacy/women-and-cardiovascular-disease . Last accessed August 2024. 10 Ray, K.K., et al. Treatment gaps in the implementation of LDL cholesterol control among high- and very high-risk patients in Europe between 2020 and 2021: the multinational observational SANTORINI study. Lancet . 2023. 29: 100624. 11 Daiichi Sankyo Europe – ETNA-AF (UK). Available at: https://www.daiichi-sankyo.eu/media/about-etna-af-uk/ . Last accessed August 2024. 12 Bul, M., et al. Frailty and oral anticoagulant prescription in adults with atrial fibrillation: A systematic review. Aging Medicine. 2022. 6(2): 195–206 13 Edoxaban Treatment in Routine Clinical Practice for Patients With Non Valvular Atrial Fibrillation (ETNA-AF-EU). Available at: https://clinicaltrials.gov/ct2/show/NCT02944019 . Last accessed August 2024. 14 Edoxaban Treatment in Routine Clinical Practice for Patients With Atrial Fibrillation in Korea and Taiwan (ETNA-AF-KOR-TWN). Available at: https://clinicaltrials.gov/ct2/show/NCT02951039 . Last accessed August 2024. 15 Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (ETNA-AF-Hong Kong). Available at: https://clinicaltrials.gov/ct2/show/NCT03247582 . Last accessed August 2024. 16 Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (NVAF). Available at: https://clinicaltrials.gov/ct2/show/NCT03247569 . Last accessed August 2024. 17 ETNA-AF-Japan. Available at: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000019728 . Last accessed August 2024.

PONTE VEDRA, Fla., March 11, 2024 /PRNewswire/ -- Cadrenal Therapeutics, Inc., (Nasdaq: CVKD), a biopharmaceutical company developing tecarfarin, a late-stage novel oral and reversible anticoagulant (blood thinner) designed to prevent heart attacks, strokes and deaths due to blood clots in patients with rare cardiovascular conditions, today provided a corporate update in connection with the filing of its Annual Report on Form 10-K for the year ended December 31, 2023. Recent Highlights Expanded focus for tecarfarin development beyond end-stage kidney disease (ESKD) with atrial fibrillation (AFib), to include patients with implanted medical devices such as left ventricular assist devices (LVADs) for heart failure as well as for the treatment of patients with antiphospholipid syndrome (APS) who require chronic anticoagulation. These two new potential rare medical conditions increase the total addressable market for tecarfarin in excess of $2 billion in the U.S. annually. Engaged The Sage Group to assist the company in exploring strategic partnerships, co-development, and licensing agreements for tecarfarin. Appointed Jeff Cole to the newly created position of Chief Operating Officer, responsible for the Company's manufacturing and supply chain operations, intellectual property, commercialization strategies, and supporting partnering activities for tecarfarin. Engaged pharmaceutical contract development and manufacturing organizations (CDMOs) to supply active pharmaceutical ingredients (API) and clinical trial materials. Highlighted recent peer-reviewed article in the Journal of the American College of Cardiology (JACC) titled, "When Direct Oral Anticoagulants Should Not Be Standard Treatment" by Antoine Bejjani, MD, et.al examined the numerous medical conditions where direct oral anticoagulants (DOACs), such as Eliquis, Xarelto, Pradaxa, and Savaysa, should not be prescribed. The article is consistent with the evolving evidence documenting the need for improved VKA-based anticoagulant therapy. Tecarfarin is the only new molecular entity (NME) that has been developed specifically to address this need. Q4 2023 operating expenses (excluding non-cash items) totaled $1,160,000. Cash used in operating activities totaled $694,000 during Q4 2023. As of December 31, 2023, cash balances were $8.5 million. Recent Reports and Presentations Noble Capital Markets initiated equity research coverage on the Company with an "Outperform" rating and a price target of US$4.00 per share. The full report by Noble Capital Markets Senior Life Sciences Analyst Robert LeBoyer can be obtained from . Douglas Losordo, M.D., Chief Medical Officer of Cadrenal, participated in a fireside chat moderated by Joe Pantginis, Ph.D., Managing Director of Research at H.C. Wainwright & Co., at the Lytham Partners 2024 Investor Select Conference. The webcast can be accessed HERE. Company presented at Biotech Showcase™ 2024, alongside the J.P. Morgan 42nd Annual Healthcare Conference. Participated in the Technology and Heart Failure Therapeutics Conference (THT 2024), which is produced by the Cardiovascular Research Foundation (CRF). Filed updated corporate slide presentation in January 2024 highlighting the opportunity for tecarfarin. Quang Pham, Founder, Chairman and Chief Executive Officer of Cadrenal Therapeutics, commented, "We believe there is a significant unmet need and market opportunity for tecarfarin in patients with rare cardiovascular conditions requiring chronic anticoagulation. Specifically, there is a lack of approved anticoagulation therapies for patients with left ventricular assist devices (LVADs), patients with end-stage kidney disease (ESKD) and atrial fibrillation (AFib), and patients with thrombotic anti-phospholipid syndrome (APS)." "During the past year, an increasing number of industry articles and presentations have concurred with our positioning, which we believe enhances our opportunity from both a regulatory and commercial perspective. We have enhanced our intellectual property protection through the application and receipt of orphan drug designations, which provides for 7 years of market exclusivity, engaged industry leaders to explore strategic partnerships, co-development and licensing agreements for tecarfarin, and have expanded our manufacturing and supply chain capabilities in preparation of an expected pivotal trial. These activities pave the way for what we believe will be an exciting year for Cadrenal." ABOUT CADRENAL THERAPEUTICS, INC. Cadrenal Therapeutics is developing tecarfarin for unmet needs in anticoagulation therapy. Tecarfarin is a late-stage novel oral and reversible anticoagulant (blood thinner) to prevent heart attacks, strokes, and deaths due to blood clots in patients with rare cardiovascular conditions. Tecarfarin has orphan drug and fast track designations from the FDA for the prevention of systemic thromboembolism (blood clots) of cardiac origin in patients with end-stage kidney disease (ESKD) and atrial fibrillation (AFib). Cadrenal is also pursuing additional regulatory strategies for unmet needs in anticoagulation therapy for patients with left ventricular assist devices (LVADs) and those with thrombotic antiphospholipid syndrome (APS). Tecarfarin is specifically designed to leverage a different metabolism pathway than the oldest and most commonly prescribed Vitamin K Antagonist (warfarin). Tecarfarin has been evaluated in eleven (11) human clinical trials and more than 1,000 individuals. In Phase 1, Phase 2, and Phase 2/3 clinical trials, tecarfarin has generally been well-tolerated in both healthy adult subjects and patients with chronic kidney disease. For more information, please visit: . Safe Harbor Statement Any statements contained in this press release about future expectations, plans, and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements." These statements include statements regarding the two new potential rare medical conditions increasing the total addressable market for tecarfarin to in excess of $2 billion in the U.S. annually, exploring strategic partnerships, co-development, and licensing agreements for tecarfarin, there being a significant unmet need and market opportunity for tecarfarin in patients with rare cardiovascular conditions requiring chronic anticoagulation, the increasing number of industry articles and presentations having concurred with the Company's positioning, enhancing the Company's opportunity from both a regulatory and commercial perspective, engaging industry leaders to explore strategic partnerships, co-development and licensing agreements for tecarfarin, 2024 being an exciting year . The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, the ability to enter into strategic partnerships, the ability to treat patients with rare cardiovascular conditions requiring chronic anticoagulation with tecarfarin, the ability to enhance the Company's opportunity from both a regulatory and commercial perspective and the other risk factors described in the Company's Annual Report on Form 10-K for the year ended December 31, 2023, and the Company's subsequent filings with the SEC, including subsequent periodic reports on Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Any forward-looking statements contained in this press release speak only as of the date hereof and, except as required by federal securities laws, the Company specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events, or otherwise. For more information, please contact: Cadrenal Therapeutics: Matthew Szot, CFO 858-337-0766 [email protected] Investors: Lytham Partners, LLC Robert Blum, Managing Partner 602-889-9700 [email protected] SOURCE Cadrenal Therapeutics, Inc.