Introduction and Objective: RAY1225, a bi-weekly GLP-1/GIP receptor agonist, has demonstrated substantial potential for glycemic control and weight loss in phase 1 study. This phase 2 trial assessed the efficacy and safety of RAY1225 compared with placebo in Chinese overweight or obese adults without diabetes. Methods: In this multicenter, randomized, double-blind, placebo-controlled phase 2 trial, nondiabetic Chinese adults with BMI ≥28 kg/m² (or 24-28 kg/m² plus comorbidity) were enrolled. Participants (N=231; mean weight 92.34 kg, BMI 32.72 kg/m², age 34.0 years, 60.1% male) were randomized to RAY1225 (3, 6, 9, 12, 15, or 18 mg) or placebo. The primary endpoint was percent body weight change from baseline to week 24. Results: Weight reduction at week 24 was dose-dependent. LS mean % changes for RAY1225 were -9.73% (3mg), -12.68% (6mg), -14.75% (9mg), -14.13% (12mg), -14.92% (15mg), and -21.18% (18mg), versus -2.96% for placebo (all p<0.001). Significantly more participants achieved ≥5%, ≥10%, and ≥15% weight loss with RAY1225. Treatment also improved waist circumference, BMI, SBP, DBP, triglycerides, and uric acid vs. placebo. The most common AEs were gastrointestinal (nausea, vomiting), with low incidence and mild-to-moderate severity. No drug-related serious AEs occurred. Conclusion: Bi-weekly RAY1225 demonstrates significant weight loss and metabolic benefits in overweight/obese nondiabetic individuals, with a favorable safety profile. Disclosure L. Ji: None. L. Yan: None. M. Xu: None. L. Gao: Consultant; Current; Innovent Biologics, Inc. X. Xia: None. C. Wang: None. Y. Zhu: None. J. Li: Employee; Current; Guangdong Raynovent Co., Ltd. Y. Peng: Employee; Current; Guangdong Raynovent Co., Ltd. H. Li: Employee; Current; Guangdong Raynovent Co., Ltd. X. Chen: Employee; Current; Guangdong Raynovent Biotech Co., Ltd.

Introduction and Objective: To investigate the efficacy, safety, and tolerability of RAY1225, a novel once every two weeks GLP-1 and GIP receptor dual agonist, in Chinese nondiabetic adults with overweight or obesity. Methods: This phase 2 double-blind, randomized, placebo-controlled trial included 2 parts. The target dose of part A was 3mg,6mg, and that of part B was 9mg and above with dose escalation and extension. Chinese nondiabetic adults with a BMI ≥28 kg/m2, or 24-28 kg/m2 accompanied by at least one obesity-related comorbidity were randomized. In part A, eligible participants were randomly assigned 1:1:1 to receive 3mg, 6 mg RAY1225 injection or placebo subcutaneously once every two weeks for 24 weeks. In part B, the randomization ratio was 4:1 to receive 9 mg (or above dose) or placebo. The primary endpoint was the percentage change from baseline to week 24 in weight. Results: A total of 132 participants were analyzed from part A and part B with dose escalated up to 9mg till now. At baseline, the mean (standard deviation) body weight was 91.07 (15.09) kg, BMI was 32.33 (3.98) kg/m2, and about 89.4% of participants had a BMI≥28 kg/m2. The mean percentage change in weight at week 24 was -10.06% (95% confidence interval, -11.63 to -8.49) with 3mg of RAY1225, -12.97% (-14.51 to -11.43) with 6mg, and -13.05% (-16.20 to -9.91) with 9mg and -3.62% (-5.19 to -2.05) with placebo (P<0.001). About 73.2% to 95.1% of participants in the RAY1225 group achieved ≥5% weight loss, compared with 30.0% in the placebo.(P<0.05). In addition, RAY1225 is also beneficial in the improvement of cardiometabolic indexes. The most common adverse events (AEs) with RAY1225 were gastrointestinal, most were mild to moderate in severity, occurring primarily during dose escalation. No drug related serious AEs occurred.. Conclusion: This study showed RAY1225 once every two weeks subcutaneous injection was safe and achieved robust body weight reduction in Chinese adults with overweight or obesity. L. Ji: None. L. Yan: None. L. Gao: Research Support; Sciwind Biosciences. M. Xu: None. X. Dong: None. C. Wang: None. Y. Zhu: None. J. Li: Employee; Guangdong Raynovent Biotech Co., Ltd. Y. Peng: Employee; Raynovent. H. Li: Employee; Guangdong Raynovent Biotech Co., Ltd. X. Chen: Employee; Guangdong Raynovent Biotech Co., Ltd.

Coronavirus disease 2019, which leads to pneumonia, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RAY1216 is a 3C-like protease inhibitor that targets SARS-CoV-2. The aim of our study was to assess the pharmacokinetics (PK) and safety of RAY1216 in healthy volunteers. This was a randomized, placebo-controlled, double-blind study consisting of four components: a single ascending dose study, a drug-drug interaction study, a multiple ascending dose study, and a food-effect study. All participants were randomly assigned to receive either a single dose or multiple doses of RAY1216 or placebo. A total of 88 healthy adult participants (male-to-female ratio of 1:1) aged 18-50 years were enrolled. A total of 37 participants (42%) experienced at least one adverse event (AE). All AEs were mild or moderate and were resolved without additional treatment. The most commonly reported adverse drug reactions were hypertriglyceridemia, hyperuricemia, and elevated serum creatinine levels. RAY1216 was well-absorbed after administration with exposure increasing in a dose-dependent manner. Food appeared to increase exposure and delay the absorption of RAY1216. Ritonavir significantly inhibited drug metabolism, and increased drug exposure increased the associated safety risks. RAY1216 was found to be well tolerated and safe in healthy participants. On the basis of preclinical results, PK characteristics, and the safety profile of RAY1216, a dosage of 400 mg three times daily was selected, thereby establishing a foundation for future research and for the clinical application of RAY1216.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05829551.

Introduction and Objective: To investigate the efficacy, safety, and tolerability of RAY1225, a novel once every two weeks GLP-1 and GIP receptor dual agonist, in Chinese adults with Type 2 diabetes (T2DM). Methods: This phase 2 double-blind, randomized, placebo-controlled trial included 2 parts. The target dose of part A was 3mg,6mg, and that of part B was 9mg and above with dose escalation and extension. Chinese T2DM adults naive or uncontrolled on Metformin, alpha-glucosidase or SGLT-2 inhibitors with a 7.0% ≤ HbA1c ≤11.0% were randomized. In part A, eligible participants were randomly assigned 1:1:1 to receive 3mg, 6mg RAY1225 or placebo subcutaneously once every two weeks for 24 weeks. In part B, the randomization ratio was 4:1 to receive 9 mg (or above dose) or placebo. The primary endpoint was the change in HbA1c at week 24. Results: A total of 132 participants were analyzed from part A and part B with dose escalated up to 9mg till now. At baseline, the mean (standard deviation) HbA1c was 8.10 (1.03) %, body weight was 77.73 (15.41) kg, BMI was 28.33 (4.18) kg/m2, and about 38.0% of participants naive to antidiabetic drugs. The reduction in HbA1c from baseline to week 24 was -1.67% (95% CI -1.91 to -1.42), -2.07% (-2.32 to -1.83), -2.24% (-2.78 to -1.70) in the 3 mg, 6mg and 9 mg, respectively, versus -0.23% (-0.47 to 0.01) with placebo (P<0.0001). More participants on RAY1225 achieved HbA1c<7% targets(80.0~100.0% Vs. 32.4%, P<0.001). All RAY1225 doses led to superior body weight reduction at week 24. In addition, RAY1225 is also beneficial in the improvement of cardiometabolic indexes. The most common adverse events (AEs) with RAY1225 were mild to moderate gastrointestinal AEs, occurring primarily during dose escalation. No severe hypoglycemia was reported, and no drug related serious AEs occurred. Conclusion: This study showed RAY1225 once every two weeks subcutaneous injection was generally well tolerated and demonstrated superior reduction in HbA1c in Chinese adults with T2DM. L. Ji: None. L. Gao: Research Support; Sciwind Biosciences. X. Dong: None. X. Huang: None. X. Zhang: None. Y. Zheng: None. C. Wang: None. L. Yan: None. J. Li: Employee; Guangdong Raynovent Biotech Co., Ltd. Y. Peng: Employee; Raynovent. H. Li: Employee; Guangdong Raynovent Biotech Co., Ltd. X. Chen: Employee; Guangdong Raynovent Biotech Co., Ltd.

Objective center dot To analyze specific immunotherapy and followup management for respiratory allergic diseases in children. Methods center dot A total of 100 children with allergic bronchial asthma admitted to our hospital from November 2020 to October 2021 were selected. Based on different treatment schemes, they were divided into two groups: the routine treatment group and the immunotherapy group, with 50 cases in each group. The routine treatment group received standard care, while the immunotherapy group underwent specific immunotherapy. Assessment parameters included asthma symptom control score, pulmonary function, immune function, levels of inflammatory factors, clinical efficacy, and adverse reactions. Results center dot After treatment and during follow-up, the immunotherapy group showed significantly lower scores for daytime and nighttime symptoms compared to the routine treatment group (P < .05). The immunotherapy group also exhibited higher FEV1/FVC and PEF% values compared to the routine therapy group after treatment and at follow-up (P < .05). Furthermore, the immunotherapy group showed higher levels of CD3+, CD4+, and CD4+/CD8+ and lower levels of CD8+ compared to the routine therapy group (P < .05). Additionally, the immunotherapy group demonstrated lower levels of IL-4 and IL-12 compared to the routine therapy group after treatment and during follow-up (P < .05). The total effective rate of the immunotherapy group was higher than that of the routine therapy group (P < .05). The incidence of adverse reactions in the immunotherapy group was similar to that in the routine therapy group (P > .05). Conclusions center dot Specific immunotherapy is a significantly effective approach to managing children's allergic bronchial asthma. It effectively controls asthma symptoms, improves lung function and immune response, and reduces inflammatory factors. It showed superior clinical efficacy and minimal adverse reactions; specific immunotherapy, therefore, is a safe and beneficial treatment option that warrants further promotion and application.

Non-alcoholic fatty liver disease is a growing health burden with limited treatment options worldwide. Herein we report a randomized, double-blind, placebo-controlled, multiple-dose trial of a first-in-class pan-phosphodiesterase inhibitor ZSP1601 in 36 NAFLD patients (NCT04140123). There were three cohorts. Each cohort included twelve patients, nine of whom received ZSP1601 50 mg once daily, 50 mg twice daily, or 100 mg twice daily, and three of whom received matching placebos for 28 days. The primary outcomes were the safety and tolerability of ZSP1601. A total of 27 (27/36, 75%) patients experienced at least one treatment-emergent adverse event (TEAE). Most TEAEs were mild to moderate. There was no Serious Adverse Event. Diarrhea, transiently elevated creatinine and adaptive headache were frequently reported adverse drug reaction. We conclude that ZSP1601 is well-tolerated and safe, showing effective improvement in liver chemistries, liver fat content and fibrosis in patients with NAFLD.

Objective To investigate the clinical efficacy of subcutaneous injection and sublingual administration of specific immunotherapy in children with allergic bronchial asthma. Methods 120 children with allergic bronchial asthma admitted to our hospital from January 2019 to January2020 were selected as the research subjects, and they were randomly divided into observation group and control group according to random number table method, with 60 cases in each group. The observation group was treated with sublingual specific treatment, and the control group was treated with subcutaneous injection. The clinical efficacy, nasal state and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group was 93.33%, which was slightly higher than 90.00% in the control group, but there was no significant difference between the two groups. Before treatment, there was no significant difference in the scores of nasal congestion, nasal itching, sneezing and runny nose between the two groups; after treatment, the scores of nasal congestion, nasal itching, sneezing and runny nose in two groups were lower than those before treatment, and the difference was statistically significant（P＜0.05）;there was no statistically significant difference in the scores of nasal state between the two groups. The incidence of adverse reactions during treatment in the observation group was 14.67%, which was lower than41.67% in the control group, and the difference was statistically significant（P＜0.05）. Conclusion Both of subcutaneous injection and sublingual administration have good therapeutic effect, but the clinical adverse reaction rate of sublingual specific treatment is low, and the clinical efficacy is more significant.

pemvidutide achieved mean weight losses of 4.9%, 10.3%, and 9.0% at the 1.2 mg, 1.8 mg**, and 2.4 mg* doses, respectively, vs. 1.6% for subjects receiving placebo (*p < 0.01, **p < 0.005 vs. placebo); subject plots at 1.8 mg (Figure) suggested sustained effects over time.MRI-PDFF analyses following 6 weeks of treatment revealed all 5 subjects with fatty liver (≥5%) at baseline, including some as high as 19.5%, receiving 1.8 mg or 2.4 mg pemvidutide had reductions in LFC to undetectable levels (limit of detection 1.5%), a >90% mean reduction. Conclusion:The rapid and potent reductions in body weight and LFC, including double-digit weight loss in 12 weeks and decreases in LFC to levels below the limit of detection, without the need for dose titration, suggest pemvidutide could be a promising new agent for treatment of NASH and its co-morbidities.

ABSTRACT Background Influenza is an acute respiratory illness. Treating with antiviral drugs can decrease the duration of illness and serious complications . ZSP1273 is a small-molecule anti-influenza drug targeting the RNA polymerase PB2 subunit of the influenza virus. The aim of this clinical trial was to evaluate the safety and pharmacokinetics (PKs) of ZSP1273 in healthy subjects. Research design and methods This was a double-blind, placebo-controlled phase 1 study consisting of three parts. 100 volunteers were enrolled and randomized to receive either single or multiple doses of ZSP1273 or placebo. Results A total of 31 (31.0%) subjects experienced at least one mild or moderate adverse event. The linear regression relationship between dose and plasma Cmax, AUC0-t, and AUC0-∞ showed an increasing trend and rapid absorption of ZSP1273. A high-fat diet had little effect on the PKs. The plasma concentration of ZSP1273 reached steady state on day 5 without drug accumulation. Conclusions ZSP1273 was safe in healthy volunteers. Based on the preclinical resuilts, safety profile and PK characteristics of ZSP1273, the dose of ZSP1273 (≥200 mg) may be used for future clinical trials in influenza patients. Trial Registration The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT03679143).

Background: The pharmacokinetics (PK), safety, and tolerability profiles of ZSP1601, a first-in-class pan-phosphodiesterase (PDE) inhibitor, were evaluated in healthy Chinese volunteers. Research design and methods: This Phase 1a study consisted of a double-blinded, randomized, placebo-controlled single ascending dose (SAD) (25 to 350 mg), multiple ascending doses (MAD) (50 or 100 mg QD), and a two-period crossover food effect study (100 mg). Results: ZSP1601 was quickly absorbed, with maximum plasma concentrations (C-max) reached at 1.25 to 2.50 h (median T-max). The exposures exhibited dose-proportional increases, while the mean half-life (t1/2) ranged from 6.34-8.64 h. Steady-state was reached within seven days in the MAD study. The mean steady trough concentrations were 423 and 588 ng/mL, respectively. ZSP1601 accumulation was low, with ratios <= 1.5. The bioavailability of ZSP1601 was equivalent under fasted and fed states. All adverse events (AEs) were assessed as mild or moderate, with headaches as the most common. The highest single doses (275 and 350 mg) yielded more AEs, yet the rates were similar with the placebo cohorts in the MAD study. Conclusions: The safety and PK profiles of ZSP1601 support further efficacy evaluation in nonalcoholic steatohepatitis patients.