ecnoglutide SC (XW003) / Sciwind Biosci, Korea Kolmar - LARVOL DELTA

Efficacy and safety of cAMP-biased GLP-1 receptor agonist ecnoglutide versus dulaglutide in patients with type 2 diabetes and elevated glucose concentrations on metformin monotherapy (EECOH-2): a 52-week, multicentre, open-label, non-inferiority, randomised, phase 3 trial. (PubMed, Lancet Diabetes Endocrinol) - P3 | "Once-weekly ecnoglutide 0·6 mg and 1·2 mg were non-inferior to dulaglutide 1·5 mg in reducing HbA1c in adults with type 2 diabetes and elevated glucose concentrations on metformin monotherapy. Although the 1·2 mg dose showed statistically significantly greater reductions in HbA1c from baseline to week 32 than dulaglutide 1·5 mg, the difference was not considered clinically relevant. Both doses of ecnoglutide were well tolerated. These results suggest that ecnoglutide might offer a new treatment option for type 2 diabetes."

Head-to-Head • Journal • Monotherapy • P3 data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

A Study of XW003 Injection in Chinese Adolescents With Obesity (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: Hangzhou Sciwind Biosciences Co., Ltd.

New P1 trial • Genetic Disorders • Obesity

A Phase II Study to Compare XW003 Injection and Semaglutide Injection in Chinese Adults With Obesity (SLIMMER-UP-SWITCH) (clinicaltrials.gov) - P2 | N=160 | Not yet recruiting | Sponsor: Hangzhou Sciwind Biosciences Co., Ltd.

New P2 trial • Genetic Disorders • Obesity

A Study to Compare XW003 Injection and Semaglutide Injection in Chinese Adults With Obesity (SLIMMER-UP-SWITCH) (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Hangzhou Sciwind Biosciences Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

VRB-101 is a potent oral GLP-1 tablet with once-weekly dosing potential (EASD 2025) - P1 | "These exposures are nearing or exceeding the weekly exposure achieved by 2.4 mg subcutaneous semaglutide or 2.4 mg subcutaneous ecnoglutide. This data supports the rationale for VRB-101 to be a QW oral GLP-1 treatment... This data supports the rationale for VRB-101 to be a QW oral GLP-1 treatment. Compared with subcutaneous injections, oral QW 90 mg and 120 mg VRB-101 are projected to match or exceed the weekly exposures of subcutaneous GLP-1 injections. VRB-101 is expected to exert potent weight lowering while improving adherence via a more patient-friendly dosing regimen."

Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A drug-drug interaction study of XW003 injection (ChiCTR) - P1 | N=56 | Completed | Sponsor: West China Second University Hospital of Sichuan University (WCSUH- SCU); West China Second University Hospital of Sichuan University (WCSUH- SCU)

New P1 trial

Chinese drug ecnoglutide surpasses Wegovy in weight loss and blood sugar control (Chosun Biz) - P3 | N=664 | NCT05813795 | Sponsor: Hangzhou Sciwind Biosciences Co., Ltd. | "Sciwind Biosciences, a biotechnology corporation based in Hangzhou, China, announced that its obesity drug candidate 'ecnoglutide' showed an average weight loss effect of over 15% within just 48 weeks....In phase 3 clinical trial results, 93% of the ecnoglutide group lost at least 5% of their body weight. This figure surpasses those shown in Chinese clinical trials for Wegovy (87%) and Monjaro (85%)."

P3 data • Obesity

VRB101 Is a Potent Oral GLP-1 Tablet with Once-Weekly Dosing Potential (ADA 2025) - "These exposures are nearing or exceeding the weekly exposure achieved by 2.4 mg subcutaneous semaglutide or 2.4 mg subcutaneous ecnoglutide. This data supports the rationale for VRB101 to be a QW oral GLP-1 treatment... This data supports the rationale for VRB101 to be a QW oral GLP-1 treatment. Compared with subcutaneous injections, oral QW 90 mg and 120 mg VRB101 are projected to match or exceed the weekly exposures of subcutaneous GLP-1 injections. VRB101 is expected to exert potent weight lowering while improving adherence via a more patient-friendly dosing regimen."

Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. (PubMed, Lancet Diabetes Endocrinol) - P3 | "In adults with obesity or overweight without diabetes (type 1 or 2), individuals administered ecnoglutide had superior and sustained reduction in bodyweight versus placebo with a favourable safety profile, supporting its potential use for weight management."

Journal • P3 data • Cardiovascular • Dyslipidemia • Genetic Disorders • Hepatology • Hypertension • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Musculoskeletal Diseases • Musculoskeletal Pain • Obesity • Orthopedics • Pain • Respiratory Diseases • Sleep Apnea • Sleep Disorder • Type 1 Diabetes Mellitus

Sciwind Biosciences Announces Publication of Phase III SLIMMER Trial Results in The Lancet Diabetes & Endocrinology and Oral Presentation at ADA Scientific Sessions (Sciwind Press Release) - P3 | N=664 | SLIMMER (NCT05813795) | Sponsor: Hangzhou Sciwind Biosciences Co., Ltd. | "Sciwind Biosciences...announced Phase III SLIMMER trial results evaluating ecnoglutide (XW003) in Chinese adults with overweight or obesity....Using the treatment policy estimand, at week 40, ecnoglutide demonstrated dose-dependent weight loss, with the highest dose (2.4 mg) achieving a mean 13.2% reduction from baseline versus a 0.1% increase for placebo (p<0.0001). By week 48, weight loss further improved to 15.4% (placebo-adjusted 15.1%), with 92.8% of participants achieving clinically meaningful ≥5% weight loss - nearly seven times the placebo response rate. Notably, 79.6% and 63.5% of participants achieved ≥10% and ≥15% weight reduction, respectively, numerically exceeding results seen with other unbiased GLP-1 therapies in similar populations. The primary and key secondary endpoints of the study showed statistically significant superiority to placebo with p-values < 0.0001."

P3 data • Obesity

A Phase 3 Study to Evaluate the Efficacy of XW003 Compared With Placebo in T2DM Patients (clinicaltrials.gov) - P3 | N=211 | Completed | Sponsor: Hangzhou Sciwind Biosciences Co., Ltd. | Active, not recruiting ➔ Completed | Trial primary completion date: Oct 2024 ➔ Jun 2024

Trial completion • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

A Drug-Drug Interaction Study Between XW003 and Metformin, Warfarin, Rosuvastatin or Digoxin (clinicaltrials.gov) - P1 | N=57 | Completed | Sponsor: Hangzhou Sciwind Biosciences Co., Ltd. | Recruiting ➔ Completed

Trial completion

A Phase 3 Study to Evaluate the Efficacy of XW003 Compared With Dulaglutide in Participants With T2DM (clinicaltrials.gov) - P3 | N=623 | Completed | Sponsor: Hangzhou Sciwind Biosciences Co., Ltd. | Active, not recruiting ➔ Completed | Trial primary completion date: Oct 2024 ➔ Jul 2024

Trial completion • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

HK inno.N to begin phase 3 trial of obesity drug in 300 patients in Korea (Korea Biomedical Review) - "HK inno.N said it has received approval from the Ministry of Food and Drug Safety to begin a phase 3 clinical trial of its investigational obesity treatment, IN-B00009 (ingredient: ecnoglutide), a glucagon-like peptide-1 receptor agonist (GLP-1 RA)....The trial will be conducted as a multicenter, randomized, double-blind, placebo-controlled, parallel-group study, with completion targeted for May 2028."

New P3 trial • Trial completion date • Obesity

A Phase 3 Study to Evaluate the Efficacy of XW003 in Adults With Overweight or Obesity (clinicaltrials.gov) - P3 | N=664 | Completed | Sponsor: Hangzhou Sciwind Biosciences Co., Ltd. | Active, not recruiting ➔ Completed | Trial completion date: Jan 2025 ➔ Oct 2024

Trial completion • Trial completion date • Genetic Disorders • Obesity

…Hanmi Pharmaceuticals to conduct phase 3 new drug trial [Google translation] (Nate) - "In addition to Hanmi Pharmaceutical, HK inno.N...submitted a phase 3 clinical trial plan for its obesity drug candidate 'IN-B00009' to the Ministry of Food and Drug Safety at the end of last year. It plans to start clinical trials next month and complete them in early 2028....Dong-A ST (170900), is conducting phase 1 clinical trials for its obesity drug 'DA-1726'. It plans to release the first clinical results in the third quarter of this year."

New P3 trial • P1 data • Trial completion date • Obesity

Efficacy and safety of GLP-1 analog ecnoglutide in adults with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 2 trial. (PubMed, Nat Commun) - "Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog...Ecnoglutide was generally safe and well tolerated. China Drug Trials Registry CTR20211014."

Clinical • Journal • P2 data • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A phase 3 evaluation of cAMP signalling biased GLP-1 analogue ecnoglutide in adults with type 2 diabetes (EASD 2024) - P3 | "Background and aims: Ecnoglutide (XW003) is a cAMP signaling biased GLP-1 analog being developed for the treatment of type 2 diabetes mellitus (T2DM) and obesity... Ecnoglutide resulted in robust HbA1c declines of up to 2.43% from baseline after 24 weeks of treatment in adults with T2DM, with up to 35.2% of participants reaching normoglycemia (HbA1c <5.7%) and 43.7% with weight reductions ≥5%."

Clinical • P3 data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Phase 3 Study to Evaluate the Efficacy of XW003 in Adults With Overweight or Obesity (clinicaltrials.gov) - P3 | N=664 | Active, not recruiting | Sponsor: Hangzhou Sciwind Biosciences Co., Ltd. | Trial primary completion date: Jan 2025 ➔ Jun 2024

Trial primary completion date • Genetic Disorders • Obesity

Biased GLP-1 Analog Ecnoglutide (XW003) Has Improved Efficacy Relative to Unbiased Peptides (ADA 2024) - "This compared to -1.14% reported for liraglutide (1.8 mg at 52 weeks), -1.55% to -1.86% for semaglutide (1.0 mg at 30-40 weeks), and -1.46% for dulaglutide (1.5 mg at 26 weeks). Bias for the cAMP pathway results in sustained signaling that correlates with increased clinical efficacy compared to unbiased GLP-1 analogs."

Clinical • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Sciwind Biosciences to Highlight Positive Results for Injectable Ecnoglutide (Phase 3), Oral Ecnoglutide (Phase 1), and Novel Amylin Analogs at the American Diabetes Association (ADA) 84th Annual Conference (PRNewswire) - P3 | N=664 | NCT05813795 | P1 | N=90 | NCT05184322 | Sponsor: Sciwind Biosciences APAC CO Pty. Ltd. | "A Phase 1 study of oral ecnoglutide (1871-LB) showed it to be safe and well tolerated and result in pronounced weight loss (up to -6.76% after 6 weeks of dosing). Improved oral bioavailability enables a 15 to 30 mg daily dose of oral ecnoglutide to match or exceed the plasma exposure of weekly subcutaneous GLP-1 analogs for weight loss. In a Phase 3 study in participants with type 2 diabetes (T2DM) (742-P, 793-P), weekly subcutaneous ecnoglutide resulted in robust HbA1c declines of up to -2.43% from baseline after 24 weeks of treatment, with up to 35.2% of participants reaching normoglycemia (HbA1c <5.7%) and 43.7% with weight reductions ≥5%....Sciwind Biosciences Co., Ltd... today announced that the company will present...at the American Diabetes Association (ADA) 84th Annual Conference."

P1 data • P3 data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Phase 3 Evaluation of cAMP Signaling Biased GLP-1 Analog Ecnoglutide (XW003) in Adults with Type 2 Diabetes (ADA 2024) - "Ecnoglutide resulted in robust HbA1c declines of up to 2.43% from baseline after 24 weeks of treatment in adults with T2DM, with up to 35.2% of participants reaching normoglycemia (HbA1c <5.7%) and 43.7% with weight reductions ≥5%."

Clinical • P3 data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Synergistic Body Weight Reduction of GLP-1 Analog Ecnoglutide and Amylin Analogs in Preclinical Animal Models (ADA 2024) - "The objective of this study was to assess the efficacy of GLP-1 analog ecnoglutide (XW003) combined with novel amylin analogs in rodent models. Amylin peptides were designed and tested in CHO-K1 CRE reporter cells expressing the amylin receptor complex (human calcitonin receptor and Ramp3) (AMY3) or calcitonin receptor alone (CTR). Novel amylin analogs (Cmpd A and Cmpd B) showed similar in vitro activities to cagrilintide. In preclinical animal models, combination of amylin analogs with GLP-1 analog ecnoglutide demonstrated a synergistic effect on body weight reduction."

Preclinical • Metabolic Disorders • Obesity

HK inno.N licenses in GLP-1 analog from Chinese biotech (Korea Biomedical Review) - "HK inno.N...announced its strategic entry into the rapidly growing global obesity treatment market through a partnership with Sciwind Biosciences, a Chinese biotech firm....This collaboration is centered around the development and commercialization of Sciwind Biosciences' glucagon-like peptide-1 (GLP-1) analog, ecnoglutide (XW003), in Korea....Under the accord, HK inno.N will make an upfront payment to Sciwind, along with milestone payments and royalties based on sales post-launch. However, the company did not disclose the size of the contract, citing contractual reasons."

Licensing / partnership • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Sciwind Biosciences Announces Positive Topline Results from Phase 3 Clinical Trial of Ecnoglutide (XW003), a Long-acting cAMP Signaling Biased GLP-1 Analog, in Adult Patients with Type 2 Diabetes in China (PRNewswire) - P3 | N=211 | NCT05680155 | Sponsor: Hangzhou Sciwind Biosciences Co., Ltd. | "Sciwind Biosciences...announced positive topline results from a Phase 3 clinical trial of ecnoglutide (XW003) in Chinese adults with type 2 diabetes mellitus (T2DM)....After 24 weeks of treatment, participants receiving ecnoglutide achieved statistically significant reductions in HbA1c. The majority of the participants receiving ecnoglutide achieved HbA1c of less than 7% (the American Diabetes Association's recommended target for people with diabetes) and a significant proportion achieved HbA1c of less than 5.7%. There were also significant body weight decreases for participants receiving ecnoglutide....Overall safety and tolerability of ecnoglutide in this study was consistent with the established profile of GLP-1 receptor agonists."

P3 data: top line • Type 2 Diabetes Mellitus