THR-β

13-Week Study to Evaluate the Safety and Efficacy of Oral VK2735 Dosed Once Daily SAN DIEGO, Jan. 8, 2025 /PRNewswire/ -- Viking Therapeutics, Inc. ("Viking") (NASDAQ: VKTX), a clinical-stage biopharmaceutical company focused on the development of novel therapies for metabolic and endocrine disorders, today announced the initiation of a Phase 2 clinical trial of the oral tablet formulation of VK2735, the company's dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. VK2375 is being developed in both oral and subcutaneous formulations for the potential treatment of various metabolic disorders such as obesity. The Phase 2 VENTURE-Oral Dosing Trial is a randomized, double-blind, placebo-controlled multicenter study designed to evaluate the safety, tolerability, pharmacokinetics and weight loss efficacy of VK2735 dosed as an oral tablet once daily for 13 weeks. The trial will enroll approximately 280 adults who are obese (BMI ≥30 kg/m2), or adults who are overweight (BMI ≥27 kg/m2) with at least one weight-related co-morbid condition. Patients will be evenly randomized to one of six dosing arms or placebo. The primary endpoint of the study is the percent change in body weight from baseline after 13 weeks of treatment. Secondary and exploratory endpoints will evaluate a range of additional safety and efficacy measures. "The VENTURE-Oral Phase 2 study represents an important milestone for the VK2735 program as we advance two formulations of this compound into later-stage development," said Brian Lian, chief executive officer of Viking Therapeutics. "Prior 28-day Phase 1 data demonstrated encouraging tolerability with the tablet formulation, as well as promising reductions in body weight. We believe VK2735's clinical results to-date suggest a differentiated profile, with the potential to provide patients and clinicians the option of two well-tolerated formulations, administered by either subcutaneous injection or as a tablet, that each utilize the same active pharmaceutical ingredient. This may reduce the potential risk of unexpected side effects and provide flexibility for use in either the induction of weight loss or for prevention of weight gain, as in a maintenance setting." Viking previously reported positive results from a 28-day Phase 1 multiple ascending dose (MAD) clinical trial of the tablet formulation of VK2735 in healthy volunteers with a BMI ≥30. Cohorts receiving VK2735 demonstrated dose-dependent reductions in mean body weight from baseline, ranging up to 8.2%. Persistent weight loss effects were observed at follow-up visits through Day 57, ranging up to 8.3% from baseline, four weeks after the last dose of VK2735 was administered. An exploratory assessment of the proportion of subjects achieving at least 5% weight loss after 28 days demonstrated that up to 100% of VK2735-treated subjects achieved ≥5% weight loss, compared with 0% for placebo. Based on a preliminary evaluation of weight loss trajectories at multiple dose levels, the company believes that continued treatment beyond 28 days may provide further reductions in body weight. In the MAD trial, oral VK2735 also demonstrated encouraging safety and tolerability through 28 days of once-daily dosing at doses up to and including 100 mg. The majority (99%) of observed treatment emergent adverse events were mild or moderate, with the majority (90%) reported as mild. Similarly, all observed gastrointestinal adverse events were reported as mild or moderate, with the majority (84%) reported as mild. Concurrent with the development of oral VK2735, Viking is also advancing a subcutaneous formulation of VK2735 through clinical development. The company previously announced positive data from the Phase 2 VENTURE study of subcutaneous VK2735, with the trial successfully achieving its primary and all secondary endpoints. Patients receiving VK2735 demonstrated statistically significant reductions in mean body weight from baseline, ranging up to 14.7%. Statistically significant differences compared to placebo were observed for all doses starting at Week 1 and were maintained throughout the course of the study. Weight loss in all treated cohorts appeared to be progressive through 13 weeks and did not show evidence of plateauing. VK2735 also demonstrated encouraging safety and tolerability in the VENTURE study, with the majority of observed adverse events being reported as mild or moderate. The company plans to initiate Phase 3 development with the subcutaneous formulation of VK2735 in the first half of 2025. About GLP-1 and Dual GLP-1/GIP Agonists Activation of the glucagon-like peptide 1 (GLP-1) receptor has been shown to decrease glucose, reduce appetite, lower body weight, and improve insulin sensitivity in patients with type 2 diabetes, obesity, or both. Semaglutide is a GLP-1 receptor agonist that has been approved by the U.S. Food and Drug Administration and is currently marketed in various dosage strengths and forms as Ozempic®, Rybelsus®, and Wegovy®. More recently, research efforts have explored the potential co-activation of the glucose-dependent insulinotropic peptide (GIP) receptor as a means of enhancing the therapeutic benefits of GLP-1 receptor activation. Tirzepatide is a dual GLP-1/GIP receptor agonist that has been approved by the U.S. Food and Drug Administration and is currently marketed in various dosage strengths and forms as Mounjaro® and Zepbound®. About Viking Therapeutics, Inc. Viking Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on the development of novel first-in-class or best-in-class therapies for the treatment of metabolic and endocrine disorders, with three compounds currently in clinical trials. Viking's research and development activities leverage its expertise in metabolism to develop innovative therapeutics designed to improve patients' lives. Viking's clinical programs include VK2735, a novel dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors for the potential treatment of various metabolic disorders. Data from a Phase 1 and a Phase 2 trial evaluating VK2735 (dosed subcutaneously) for metabolic disorders demonstrated an encouraging safety and tolerability profile as well as positive signs of clinical benefit. Concurrently, the company is evaluating an oral formulation of VK2735 in a Phase 2 trial. Viking is also developing VK2809, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the treatment of lipid and metabolic disorders. The compound successfully achieved both the primary and secondary endpoints in a recently completed Phase 2b study for the treatment of biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis. In a Phase 2a trial for the treatment of non-alcoholic fatty liver disease (NAFLD) and elevated LDL-C, patients who received VK2809 demonstrated statistically significant reductions in LDL-C and liver fat content compared with patients who received placebo. The company's newest program is evaluating a series of internally developed dual amylin and calcitonin receptor agonists (or DACRAs) for the treatment of obesity and other metabolic disorders. In the rare disease space, Viking is developing VK0214, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the potential treatment of X-linked adrenoleukodystrophy (X-ALD). In a Phase 1b clinical trial in patients with the adrenomyeloneuropathy (AMN) form of X-ALD, VK0214 was shown to be safe and well-tolerated, while driving significant reductions in plasma levels of very long-chain fatty acids (VLCFAs) and other lipids, as compared to placebo. For more information about Viking Therapeutics, please visit . Forward-Looking Statements This press release contains forward-looking statements regarding Viking Therapeutics, Inc., under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including statements about Viking's expectations regarding its clinical and preclinical development programs, anticipated timing for reporting clinical data and cash resources. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and adversely and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: risks associated with the success, cost and timing of Viking's product candidate development activities and clinical trials, including those for VK2735, VK0214, VK2809, and the company's other incretin receptor agonists; risks that prior clinical and preclinical results may not be replicated; risks regarding regulatory requirements; and other risks that are described in Viking's most recent periodic reports filed with the Securities and Exchange Commission, including Viking's Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent Quarterly Reports on Form 10-Q, including the risk factors set forth in those filings. These forward-looking statements speak only as of the date hereof. Viking disclaims any obligation to update these forward-looking statements except as required by law. SOURCE Viking Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

In a head-to-head diet-induced obese (DIO) mouse study, ASC47 low dose combination 1 (ASC47, 3 mg/kg, subcutaneous (SQ), once every four weeks plus semaglutide, 30 nmol/kg, SQ, once daily), demonstrated superior weight loss compared to semaglutide monotherapy (30 nmol/kg, SQ, once daily), showing an average total body weight reduction of 36.2% compared to 23.1%, a 56.7% greater reduction in body weight compared to semaglutide monotherapy. Human equivalent dose of ASC47 low dose 1 (3 mg/kg, SQ, once every four weeks) in mice is estimated to be approximately 20 mg based on the body surface area conversion. Interim data from a Phase I single ascending dose (SAD) study in Australia in subjects with elevated low-density lipoprotein cholesterol (LDL-C) showed that ASC47, via SQ injection, demonstrated a good tolerability profile up to 90 mg. The Australian SAD study is still ongoing with higher doses of ASC47. ASC47 low dose combinations with semaglutide restored the body composition of obese mice to the level of healthy non-obese mice. At the end of treatment, the percentage of total muscle mass over the total body weight of obese mice treated with ASC47 low dose combination treatments (68.8%) was similar to healthy non-obese mice (66.0%), indicating healthy weight loss. Semaglutide monotherapy was unable to restore body composition to healthy levels. ASC47 low dose combination treatments were well tolerated in obese mice and exhibited a statistically significant reduction in levels of liver enzymes such as alanine aminotransferase (ALT) compared to vehicle treatment in obese mice. HONG KONG, Dec. 18, 2024 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX:1672, "Ascletis") announces encouraging efficacy results from its study in diet-induced obese (DIO) mice combining ASC47, a first-in-class muscle-preserving weight loss drug candidate for the treatment of obesity, with semaglutide. ASC47 is an adipose-targeted, once-monthly subcutaneously (SQ) injected thyroid hormone receptor beta (THRβ) selective small molecule agonist, discovered and developed in-house at Ascletis. ASC47 possesses unique and differentiated properties to enable adipose targeting, resulting in dose-dependent high drug concentrations in the adipose tissue. Interim data from a Phase I single ascending dose (SAD) study in Australia in subjects with elevated low-density lipoprotein cholesterol (LDL-C) (NCT06427590) showed that ASC47, via SQ injection, demonstrated a half-life of 21 days. Further, ASC47 demonstrated a good tolerability profile up to 90 mg with no serious adverse events (SAEs) and no discontinuations due to adverse events (AEs). The majority of AEs were mild (grade 1). There were no gastrointestinal or cardiac AEs reported, as well as no abnormal liver enzymes reported (Link). The Australian SAD study is still ongoing with higher doses of ASC47. In previous preclinical studies, ASC47 regular dose (45 mg/kg, SQ, once every two weeks) monotherapy demonstrated total body weight reduction of 24.6%, similar to semaglutide monotherapy (23.1%, 30 nmol/kg, SQ, once daily). ASC47 regular dose increased total muscle mass by 5.8%, compared to a decline in total muscle mass of 9.3 % for semaglutide (Link). Detailed Preclinical Data of ASC47 Low Dose Combinations The objective of the head-to-head ASC47 low dose combination DIO mouse study was to compare ASC47 low doses (3 mg/kg or 9 mg/kg) and low frequency (SQ, once every four weeks) combined with semaglutide (30 nmol/kg, SQ, once daily) against semaglutide monotherapy (30 nmol/kg, SQ, once daily). ASC47 low dose combination 1 (ASC47, 3 mg/kg, SQ, once every four weeks plus semaglutide, 30 nmol/kg, SQ, once daily) treatment was superior to semaglutide monotherapy (30 nmol/kg, SQ, once daily), showing an average total body weight reduction of 36.2% compared to 23.1%, achieving 56.7% more relative weight loss compared to semaglutide monotherapy (Table 1). Table 1. ASC47 low dose combination treatments demonstrated superior weight loss to semaglutide monotherapy Note: Treatment duration: 28 days; Obese mice: diet-induced obese mice; SQ: subcutaneous; QD: once daily; Q4W: once every four weeks Human equivalent dose of ASC47 low dose 1 (3 mg/kg, SQ, once every four weeks) in mice is estimated to be approximately 20 mg based on the body surface area conversion. Interim data from a Phase I single ascending dose (SAD) study in Australia in subjects with elevated LDL-C showed that ASC47, via SQ injection, demonstrated a good tolerability profile up to 90 mg. The Australian SAD study is still ongoing with higher doses of ASC47. ASC47 low dose combinations with semaglutide restored the body composition of obese mice to the level of healthy non-obese mice. At the end of treatment, the percentage of total muscle mass over the total body weight of obese mice treated with ASC47 low dose combination treatments (68.8%) was similar to healthy non-obese mice (66.0%), indicating healthy weight loss. Semaglutide monotherapy was unable to restore body composition to healthy levels (Table 1). Cumulative caloric intake of obese mice with ASC47 low dose combination treatments at the end of treatment was statistically higher than that of obese mice with semaglutide monotherapy treatment (Table 1), suggesting that ASC47 has different mechanisms of action from incretin-based drugs. ASC47 low dose combination treatments were well tolerated in obese mice and exhibited a statistically significant reduction in levels of liver enzymes such as alanine aminotransferase (ALT) compared to vehicle treatment in obese mice (Table 2). Table 2. ASC47 low dose combination treatments demonstrated statistically significant ALT reduction compared to vehicle treatment in obese mice Note: Treatment duration: 28 days; Obese mice: diet-induced obese mice; SQ: subcutaneous; QD: once daily; Q4W: once every four weeks Both ASC47 low doses statistically and significantly reduced fasting blood glucose, cholesterol and LDL-C compared to vehicle treated obese mice (Table 3). Table 3. ASC47 low dose treatments demonstrated statistically significant decreases in fasting blood glucose, cholesterol and LDL-C compared to vehicle treated obese mice Note: Treatment duration: 28 days; Obese mice: diet-induced obese mice; SQ: subcutaneous; QD: once daily; Q4W: once every four weeks In obese mice, ASC47 low dose combination treatments reduced statistically and significantly more fasting blood glucose, cholesterol and LDL-C than semaglutide monotherapy treated obese mice (Table 4). Table 4. ASC47 low dose combination treatments demonstrated superior fasting blood glucose, cholesterol and LDL-C reductions compared to semaglutide monotherapy Note: Treatment duration: 28 days; Obese mice: diet-induced obese mice; SQ: subcutaneous; QD: once daily; Q4W: once every four weeks "We are excited by these data showing that adipose-targeted ASC47 low dose combination treatments achieved 56.7% more relative weight loss compared to semaglutide monotherapy. Importantly, in the preclinical study, adipose-targeted ASC47 low dose combination treatments produced healthy weight loss, increasing our confidence that ASC47-based combination therapies may clinically improve weight loss and muscle preservation compared to incretin-based drugs alone," said Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis, " Unlike liver enzyme elevations observed with an apelin receptor (APJ) agonist, low doses of ASC47 in combination with an incretin-based drug showed statistically significant reductions in liver enzymes. We are advancing development of ASC47 as both a monotherapy at regular doses and a combination therapy at low doses for the treatment of obesity and other metabolic diseases." Ascletis Obesity Portfolio ASC47 is an adipose-targeted, once-monthly subcutaneously injected THRβ selective small molecule agonist. Interim data from a Phase I single ascending dose (SAD) study in Australia in subjects with elevated low-density lipoprotein cholesterol (LDL-C) (NCT06427590) have been released. ASC47 is currently in the clinical trials of patients with obesity in Australia, with topline data of Phase IIa study expected in the second quarter of 2025. In addition to ASC47, Ascletis is also developing ASC30, a GLP-1 receptor (GLP-1R) biased small molecule that can be dosed once daily orally or once monthly subcutaneously. Both ASC30 once-daily oral tablet (NCT06680440) and ASC30 once-monthly SQ injection (NCT06679959) are currently in Phase Ib clinical trials in the U.S. for the treatment of obesity, with topline data expected in the first quarter of 2025. About Ascletis Pharma Inc. Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK), covering the entire value chain from discovery and development to GMP manufacturing. Led by a management team with deep expertise and a proven track record, Ascletis has rapidly advanced its pipeline, focusing on two therapeutic areas with unmet medical needs from a global perspective: metabolic diseases and viral diseases. Ascletis has multiple clinical stage drug candidates in its R&D pipeline. For more information, please visit . Contact: Peter Vozzo ICR Healthcare 443-231-0505 (U.S.) [email protected] Ascletis Pharma Inc. PR and IR teams +86-181-0650-9129 (China) [email protected] [email protected] SOURCE Ascletis Pharma Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

New recommendations on nutrition, weight-loss medications and technology ARLINGTON, Va., Dec. 9, 2024 /PRNewswire/ -- Today, the American Diabetes Association® released the Standards of Care in Diabetes—2025 (Standards of Care) the gold standard in evidence-based guidelines for diagnosing and managing diabetes and prediabetes. Based on the latest scientific research and clinical trials, the Standards of Care includes strategies for diagnosing and treating diabetes in both youth and adults, methods to prevent or delay type 2 diabetes and its associated comorbidities like obesity, and care recommendations to enhance health outcomes. Continue Reading Diabetes Care Volume 48 Supplement 1: Standards of Care in Diabetes 2025 "The latest ADA guidelines combine comprehensive, evidence-based recommendations for diabetes care with actionable guidance to enable health care professionals provide the best care possible for those living with diabetes," said Nuha El Sayed, MD, MMSc, the ADA's senior vice president of health care improvement. Notable updates to the Standards of Care in Diabetes—2025 include: Consideration of continuous glucose monitor (CGM) use for adults with type 2 diabetes on glucose-lowering agents other than insulin. Guidance on actions to take during circumstances of medication unavailability, such as medication shortages. Additional guidance on the use of GLP-1 receptor agonists beyond weight loss for heart and kidney health benefits. Guidance on continuation of weight management pharmacotherapy beyond reaching weight loss goals. Guidance for treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) with moderate or advanced liver fibrosis using a thyroid hormone receptor-beta agonist. Emphasis on the use of antibody-based screening for presymptomatic type 1 diabetes in those who have a family history or known genetic risk. Guidance on the use of recreational cannabis for type 1 diabetes and those with other forms of diabetes at risk for diabetic ketoacidosis (DKA). Key updates highlighting potentially harmful medications in pregnancy and guidance for appropriately modifying the care plan. Expanded nutrition guidance to encourage evidence-based eating patterns, including those incorporating plant-based proteins and fiber, that keep nutrient quality, total calories, and metabolic goals in mind. The ADA annually updates its Standards of Care through the efforts of its Professional Practice Committee (PPC). Comprising global experts from diverse professional backgrounds, the PPC includes physicians, nurse practitioners, certified diabetes care and education specialists, registered dietitian nutritionists, pharmacists, and methodologists. Its members hold expertise in a range of related fields. The 2025 Standards of Care has garnered endorsements from the American College of Cariology (Section 10), the American Geriatrics Society (Section 13), the American Society of Bone and Mineral Research (Bone Health, Section 4), and the Obesity Society (Section 8). Other noteworthy changes include: Emphasis on water intake over nutritive and nonnutritive sweetened beverages; and the use of nonnutritive sweeteners over sugar-sweetened products in moderation and for the short term to reduce overall calorie and carbohydrate intake. Importance of meeting resistance training guidelines for those treated with weight management pharmacotherapy or metabolic surgery. Guidance for DKA and hyperglycemic hyperosmolar state (HHS) in the outpatient and inpatient settings. Screening updates for fear of hypoglycemia, diabetes distress, and anxiety. Improved approach for diabetes care delivery for older adults. Guidance on the use of GLP-1 receptor agonists and dual GIP and GLP-1 receptor agonists in the perioperative care setting. "Improving the lives of people affected by diabetes is a key part of the ADA's mission. The Standards of Care offers the trusted support needed for people living with diabetes and those caring for them to manage the disease and thrive until we find a cure," said Charles "Chuck" Henderson, the ADA's chief executive officer. The Standards of Care in Diabetes—2025 is now available online as a supplement to the January 2025 issue of Diabetes Care®. In addition, a convenient Standards of Care app, available for iOS and Android systems, offers the latest guidelines with interactive tables and algorithms for easy reference. Additional resources, including a comprehensive slide deck and a webcast offering continuing education (CE) credit, are available on the ADA's professional website DiabetesPro®. A quick-reference pocket chart will soon be available for purchase on ShopDiabetes.org. For primary care providers, the Abridged Standards of Care, developed by the ADA's Primary Care Advisory Group, is planned for release in Spring 2025 in Clinical Diabetes®. Through the "living" Standards of Care process, the online version, abridged guidelines, and all related materials will be updated in real time throughout the year to reflect the latest evidence and regulatory changes. About the American Diabetes Association The American Diabetes Association (ADA) is the nation's leading voluntary health organization fighting to end diabetes and helping people thrive. For 84 years, the ADA has driven discovery and research to prevent, manage, treat, and ultimately cure diabetes. There are 136 million Americans living with diabetes or prediabetes. Through advocacy, program development, and education, we're fighting for them all. To learn more or to get involved, visit us at diabetes.org or call 1-800-DIABETES (800-342-2383). Join the fight with us on Facebook (American Diabetes Association), Spanish Facebook (Asociación Americana de la Diabetes), LinkedIn (American Diabetes Association), and Instagram (@AmDiabetesAssn). To learn more about how we are advocating for everyone affected by diabetes, visit us on X (@AmDiabetesAssn). Contact: [email protected] SOURCE American Diabetes Association WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED