Hangzhou Normal University

Psychologists asked experiment participants to choose to receive $40 in seven days or $60 in 30 days, for example, under a variety of time constraints. The experiment showed that people tend to make more impulsive decisions if they think about time delays first, and more patient decisions if they think about the greater reward associated with waiting longer. The findings could be applied where people are being encouraged to make life choices that will benefit them in the long run, such as eating healthier, exercising or saving for retirement, by emphasizing the future large rewards and deemphasizing how long it will take to see them. If you had to decide whether to receive $40 in seven days or $60 in 30 days, which would you choose? Your answer could have less to do with whether you are a patient or impatient person than with how the choice is presented, according to a new paper published in Nature Communications. The research found that first revealing the time delay -- seven to 30 days -- made people tend to prefer the shorter-term, "impatient" option, while first revealing the greater reward of the 30-day option encouraged people to choose the "patient" option of waiting to receive more money. The amount of time allotted to decide also influences their choices, but not always in the way you might expect. In some cases, people were more patient when they had less time to decide. "The takeaway message is that people can be impatient or exhibit a lack of self-control for many reasons," said corresponding author Ian Krajbich, an associate professor of psychology at UCLA. "It may in part reflect their true patience but it may also be due to attentional biases, like how prominently delay information is presented. Immediately focusing on the benefits of waiting might help people improve their self-control." Krajbich, who studies the cognitive process by which people make choices, and colleagues at Zhejiang University and Hangzhou Normal University, led by Fadong Chen, asked a total of 353 college student volunteers to choose between patient and impatient alternatives, for example to receive $40 in seven days or $60 in 30 days, by clicking their choice on a computer screen while software tracked and recorded the movements of their mouse. In some cases, participants had to make their decisions in two seconds, in others they had unlimited time or had to wait 10 seconds before choosing. At the end of the study, participants earned money based on one decision. Whether the mouse shot straight to one of the options or wandered a little as the participant considered their options revealed the order in which they were considering dimensions of the task, and at what point in time their mouse movements were first influenced by either the delays or rewards. More than half the participants patiently chose the "larger later" option regardless of time constraint: "If you're somebody who focuses on the rewards first, time pressure accentuates that and makes you more patient," Krajbich said. "And if you're a little impatient by nature and focus on delays first, time pressure magnifies that impatience. Time pressure has different effects for different people. It enhances inherent bias." But the researchers found that they could manipulate that bias by changing how they presented information about the choices. The researchers then repeated the experiments, but altered how the information was presented, sometimes revealing the delay first and sometimes revealing the rewards first. In these experiments, participants were allowed to make choices at various times, such as after seeing just one piece of information or after seeing them all. These experiments revealed that when shown the rewards first, participants made more "larger later" choices. When the time delay was presented first, they made more "smaller sooner" choices. People were more patient when they saw rewards before delays. Research on decision-making has shown that when people are making decisions, they have to evaluate their options over time because they often don't immediately know what to do. Because people have limited attention, they tend to focus on one dimension of the choice at a time. In the experiments, these two dimensions were delay or reward, and participants tended to consider the amounts first and then the delays, but this varied across people. Those who were less patient in their choices were more likely to consider the delays first. "If people consider amounts first, they're more likely to choose the patient option, and if they consider the delays first, they're more likely to choose the impatient option. If you're trying to get people to be more patient by getting them to slow down or speed up their decisions, you need to know which dimension they're going to focus on first. That will determine the appropriate intervention," Krajbich said. The findings could be applied where people are being encouraged to make life choices that will benefit them in the long run, such as eating healthier, exercising or saving for retirement. "You want to emphasize those future large rewards and try to deemphasize how long it's going to take," Krajbich said. "Try to have the reward information come first."

-- ASC41 is ranking first in China and third in the world in terms of clinical progress as a thyroid hormone receptor β (THRβ) agonist drug candidate for non-alcoholic steatohepatitis (NASH). ASC41 Phase II clinical trial is currently the most advanced 52-week Phase II clinical trial which is initiated by a China biotech company with enrollment of liver biopsy-proven NASH patients -- The Phase II clinical trial will enroll approximately 180 liver biopsy-proven NASH patients to be randomized into two treatment arms and one placebo control arm at the ratio of 1:1:1 with oral administration of ASC41 (2 mg or 4 mg) or placebo once daily for 52 weeks. The enrollment is expected to be completed in the third quarter of 2023 -- The primary endpoint of the Phase II clinical trial is non-alcoholic fatty liver disease (NAFLD) activity score (NAS) improvement ≥2 points (improvement in inflammation or ballooning) and no worsening of fibrosis HANGZHOU and SHAOXING, China, Oct. 4, 2022 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX: 1672, "Ascletis") announces dosing of the first patient in the 52-week Phase II clinical trial of thyroid hormone receptor β (THRβ) agonist ASC41 for treatment of liver biopsy-proven non-alcoholic steatohepatitis (NASH) patients. ASC41 Phase II clinical trial is currently the most advanced 52-week Phase II clinical trial which is initiated by China biotech company with enrollment of liver biopsy-proven NASH patients. The randomized, double-blind, placebo-controlled and multi-center Phase II clinical trial intends to evaluate the safety and efficacy of ASC41 for treatment of liver biopsy-proven NASH patients, and will enroll approximately 180 liver biopsy-proven NASH patients to be randomized into two treatment arms and one placebo control arm at the ratio of 1:1:1 with oral administration of ASC41 (2 mg or 4 mg) or placebo once daily for 52 weeks. The enrollment is expected to be completed in the third quarter of 2023. ASC41 is a liver-targeted prodrug, and its active metabolite is a selective THRβ agonist. THRβ is highly expressed in the liver, and THRβ agonists have demonstrated to be active in reducing low density lipoprotein (LDL), triglyceride (TG) and hepatic steatosis in humans. By promoting fatty acid breakdown and stimulating mitochondrial biogenesis, THRβ helps to reduce lipotoxicity and improve liver function, thereby reducing liver fat. In January 2021, Ascletis announced the completion of a randomized, double-blind, placebo controlled single- and multiple-ascending dose Phase I clinical trial in 65 subjects with elevated low-density lipoprotein cholesterol (LDL-C) (>110 mg/dL), in which subjects demonstrated clinically meaningful and statistically significant reduction in LDL-C and TG compared with placebo after 14 days treatment of once daily oral dosing of ASC41 tablet. At a very low dose of 1 mg, placebo-adjusted relative TG reduction from baseline was 39% (P=0.002) (). Compared with THRβ agonist Resmetirom (MGL-3196), ASC41 has higher potency and requires lower dosage (1 mg) to reach over 30% relative TG reduction as placebo-adjusted. In February 2021, Ascletis announced positive clinical results in overweight and obese subjects for ASC41. Preliminary data suggested that over 28 days of oral dosing of ASC41, subjects demonstrated sustainable, clinically meaningful and statistically significant reduction in LDL-C, TG and total cholesterol (TC), compared with placebo. High-density lipoprotein cholesterol (HDL-C) remained relatively unchanged (). In September 2021, Ascletis completed the U.S. Phase I trial of drug-drug interactions in healthy subjects and pharmacokinetics (PK) in patients with non-alcoholic fatty liver disease (NAFLD) for ASC41 oral tablets. ASC41 is mainly metabolized by CYP3A4 to form an active metabolite ASC41-A, a selective THRβ agonist. This clinical study results demonstrated that clinically significant drug-drug interactions would be unlikely between ASC41/ASC41-A and antidepressants (selective-serotonin/serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs), most of them are mild/moderate CYP3A4 inhibitors), which are commonly used in NASH patient population. It also revealed that the PK of ASC41/ASC41-A in healthy volunteers was not significantly different from that in patients with NAFLD (). "Non-alcoholic fatty liver disease (NAFLD) has become one of the most important causes of chronic liver disease, with a prevalence of 25% globally[1], one-fifth of which will progress to non-alcoholic steatohepatitis (NASH). NASH will become the major cause of liver transplant in a decade. According to statistics, there will be 48.26 million and 27 million NASH patients in China and the U.S. in 2030 [1], respectively. Despite the huge patient population, the U.S. Food and Drug Administration, European Medicines Agency and China National Medical Products Administration have not approved any NASH treatment, which indicates a huge unmet medical need. THRβ is a promising therapeutic target for treatment of NASH. Studies have shown that THRβ agonist can significantly improve NASH and inflammation[2]. I'm looking forward to advancing the clinical study and bringing more benefits to NASH patients." Said Dr. Junping Shi, Deputy Dean of the Affiliated Hospital of Hangzhou Normal University, Advisor of National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association and principal investigator of ASC41-NASH. "Ascletis is at the frontier of NASH research in China and even in the world. Leveraging in-house R&D capabilities and global cooperation, Ascletis has established a broad pipeline of NASH candidates. Addition to the three promising single-drug candidates targeting fatty acid synthase (FASN), thyroid hormone receptor β (THRβ) and farnesol X receptor (FXR), respectively, Ascletis also developed three combination therapies. Dosing the first biopsy-proven NASH patient in ASC41 Phase II clinical trial marks a great milestone to us. Meanwhile, ASC40 (FASN), Ascletis' another NASH candidate will update topline results of interim analysis from the Phase IIb clinical trial in biopsy-proven NASH patients in the fourth quarter, 2022. All these progresses once again demonstrate our in-depth insights and strong R&D capabilities. We will continue to advance clinical studies of our NASH pipeline and bring more benefits to patients worldwide." said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis. About Ascletis 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 manufacturing and commercialization. Led by a management team with deep expertise and a proven track record, Ascletis focuses on three therapeutic areas with unmet medical needs from a global perspective: viral diseases, non-alcoholic steatohepatitis (NASH) and oncology. Through excellent execution, Ascletis rapidly advances its drug pipeline with an aim of leading in global competition. To date, Ascletis has three marketed products, i.e. ritonavir tablets, GANOVO® and ASCLEVIR®, and 20 drug candidates in its R&D pipeline. The most advanced drug candidates include ASC22 (HBV functional cure), ASC10 and ASC11(oral small molecules for COVID-19 treatment), ASC40 (recurrent glioblastoma), ASC42 (PBC, primary biliary cholangitis), and ASC40 (acne). For more information, please visit . SOURCE Ascletis Pharma Inc.