A Single-Center, Open-Label Study to Evaluate the Effect of XW003 Injection on the Pharmacokinetics of Metformin, Warfarin, Rosuvastatin or Digoxin in Healthy Subjects

This is a study of a drug-drug interaction between XW003 and Metformin, Warfarin, Rosuvastatin or Digoxin

Start Date14 Jul 2023

Sponsor / Collaborator

Hangzhou Sciwind Biosciences Co., Ltd.Startup

100 Clinical Results associated with Ecnoglutide

100 Translational Medicine associated with Ecnoglutide

100 Patents (Medical) associated with Ecnoglutide

Literatures (Medical) associated with Ecnoglutide

01 Sep 2023·Molecular metabolism

Discovery of ecnoglutide - A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog.

Article

Author: Wang, Bin ; Adegbite, Eric ; Zou, Haixia ; Feng, Jing ; Qin, Hong ; Zheng, Qing ; Li, Feng ; Pan, Hai ; Zhong, Weidong ; Junaidi, Mohammed K ; Xu, Zheng ; Xu, Susan ; Jones, Catherine L ; Zhu, Rui ; Guo, Wanjun ; Li, Yao ; Li, Yan ; Fenaux, Martijn ; Zhu, Zhiyi ; Hao, Sujuan ; Telusca, Libnir

OBJECTIVE:

Glucagon-like peptide (GLP)-1 is an incretin hormone that acts after food intake to stimulate insulin production, enhance satiety, and promote weight loss. Here we describe the discovery and characterization of ecnoglutide (XW003), a novel GLP-1 analog.

METHODS:

We engineered a series of GLP-1 peptide analogs with an alanine to valine substitution (Ala8Val) and a γGlu-2xAEEA linked C18 diacid fatty acid at various positions. Ecnoglutide was selected and characterized in GLP-1 receptor signaling assays in vitro, as well as in db/db mice and a diet induced obese (DIO) rat model. A Phase 1, double-blind, randomized, placebo-controlled, single (SAD) and multiple ascending dose (MAD) study was conducted to evaluate the safety, tolerability, and pharmacokinetics of subcutaneous ecnoglutide injection in healthy participants. SAD doses ranged from 0.03 to 1.0 mg; MAD doses ranged from 0.2 to 0.6 mg once weekly for 6 weeks (ClinicalTrials.gov Identifier: NCT04389775).

RESULTS:

In vitro, ecnoglutide potently induced cAMP (EC₅₀ = 0.018 nM) but not GLP-1 receptor internalization (EC₅₀ > 10 μM), suggesting a desirable signaling bias. In rodent models, ecnoglutide significantly reduced blood glucose, promoted insulin induction, and led to more pronounced body weight reduction compared to semaglutide. In a Phase 1 trial, ecnoglutide was generally safe and well tolerated as a once-weekly injection for up to 6 weeks. Adverse events included decreased appetite, nausea, and headache. The half-life at steady state ranged from 124 to 138 h, supporting once-weekly dosing.

CONCLUSIONS:

Ecnoglutide showed a favorable potency, pharmacokinetic, and tolerability profile, as well as a simplified manufacturing process. These results support the continued development of ecnoglutide for the treatment of type 2 diabetes and obesity.

01 Jul 2022·Molecular and cellular endocrinology

Corrigendum to “Recombinant human glucagon-like peptide-1 protects against chronic intermittent hypoxia by improving myocardial energy metabolism and mitochondrial biogenesis” [Mol. Cell Endocrinol. 481(2019) 95–103]

Author: Yang, Xiaoyu ; Tao, Lichan ; Wang, Long ; Jiang, Xiaohong ; Hua, Fei

01 May 2019·Journal of diabetes investigationQ3 · MEDICINE

Protein kinase C and protein kinase A are involved in the protection of recombinant human glucagon‐like peptide‐1 on glomeruli and tubules in diabetic rats

Q3 · MEDICINE

ArticleOA

Author: Wang, Zai ; Jiang, Yongwei ; Zhao, Wanni ; Lou, Jinning ; Xu, Shiqing ; Peng, Liang ; Fang, Qing ; Zhang, Wenjian ; Deng, Tingting ; Yin, Weiqin

Abstract:

Aims/Introduction:

Blockade or reversal the progression of diabetic nephropathy is a clinical challenge. The aim of the present study was to examine whether recombinant human glucagon‐like peptide‐1 (rhGLP‐1) has an effect on alleviating urinary protein and urinary albumin levels in diabetic rats.

Materials and Methods:

Streptozotocin‐induced diabetes rats were treated with rhGLP‐1 insulin and saline. Using immunostaining, hematoxylin–eosin, electron microscopy and periodic acid–Schiff staining to study the pathology of diabetic nephropathy, and we carried out quantitative reverse transcription polymerase chain reaction, western blot and immunohistochemistry to identify the differentially expressed proteins. The mechanism was studied through advanced glycation end‐products‐induced tubular epithelial cells.

Results:

rhGLP‐1 inhibits protein kinase C (PKC)‐β, but increases protein kinase A (PKA), which reduces oxidative stress in glomeruli and in cultured glomerular microvascular endothelial cells. In tubules, rhGLP‐1 increased the expression of two key proteins related to re‐absorption – megalin and cubilin – which was accompanied by downregulation of PKC‐β and upregulation of PKA. On human proximal tubular epithelial cells, rhGLP‐1 enhanced the absorption of albumin, and this was blocked by a PKC activator or PKA inhibitor.

Conclusions:

These findings suggest that rhGLP‐1 can reverse diabetic nephropathy by protecting both glomeruli and tubules by inhibiting PKC and activating PKA.

News (Medical) associated with Ecnoglutide

21 Jun 2024

·www.prnewswire.com

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

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%. Novel amylin analogs ( 788-P, 789-P) were identified that showed potent in vitro activity. In preclinical models, combination of amylin analogs with ecnoglutide demonstrated a synergistic effect on body weight reduction, with improved efficacy compared to combination of cagrilintide and semaglutide. Moreover, a novel amylin development candidate was identified that is stable at neutral pH, providing the opportunity to co-formulate with ecnoglutide or other GLP-1 analogs to improve ease of use for patients and reduce costs. HANGZHOU, China and SAN FRANCISCO, June 21, 2024 /PRNewswire/ -- Sciwind Biosciences Co., Ltd., a clinical-stage biopharmaceutical company focusing on discovering and developing innovative therapies to treat metabolic disease, today announced that the company will present positive results from a Phase 3 clinical study of injectable ecnoglutide (XW003) in T2DM patients and from a Phase 1 study for oral ecnoglutide (XW004) in healthy and healthy obese participants, as well as preclinical data for novel amylin analog programs, at the American Diabetes Association (ADA) 84th Annual Conference. Five posters, including one late-breaking poster, will be presented. The ADA conference is being held in Orlando, FL June 21-24, 2024. Late Breaking Poster Presentation (1871-LB): Saturday June 22, 12:30 PM - 1:30 PM "Phase 1 Topline Safety, Efficacy, and Pharmacokinetics of Oral Ecnoglutide" Poster Presentation (742-P): Sunday June 23, 12:30 PM - 1:30 PM "A Phase 3 Evaluation of cAMP Signaling Biased GLP-1 Analog Ecnoglutide (XW003) in Adults with Type 2 Diabetes" Poster Presentation (793-P): Sunday June 23, 12:30 PM - 1:30 PM "Biased GLP-1 analog ecnoglutide (XW003) has improved efficacy relative to unbiased peptides" Poster Presentation (789-P): Sunday June 23, 12:30 PM - 1:30 PM "Discovery of a Novel, Long-Acting Amylin Receptor Agonist for Body Weight Control" Poster Presentation (788-P): Sunday June 23, 12:30 PM - 1:30 PM "Synergistic Body Weight Reduction of GLP-1 Analog Ecnoglutide and Amylin Analogs in Preclinical Animal Models" About ecnoglutide Glucagon-like peptide-1 (GLP-1) analogs are effective therapies in managing type 2 diabetes, obesity, and have demonstrated clinical potential as a treatment for MASH. Ecnoglutide is a novel, biased, long-acting GLP-1 peptide analog optimized for improved biological activity, cost-effective manufacturing, and once weekly subcutaneous dosing. Ecnoglutide has demonstrated treatment benefits for patients with type 2 diabetes and obesity and is safe and well tolerated in Phase 1 through Phase 3 clinical studies. About Sciwind Sciwind Biosciences is a clinical stage biopharmaceutical company focusing on discovering and developing innovative therapies to treat metabolic disease. Its product pipeline consists of potentially first-in-class and best-in-class drug candidates, including the long-acting GLP-1 peptide analog XW003 (Phase 3), oral GLP-1 peptide analog XW004 (Phase 1), an oral small molecule GLP-1 receptor agonist XW014 (Phase 1), and novel amylin analogs (preclinical). Sciwind has developed multiple proprietary technologies, including oral peptide and inhaled protein therapeutic delivery platforms and identified a series of drug candidates based on these core platform technologies. For more information, visit . SOURCE Hangzhou Sciwind Biosciences Co., Ltd.

Clinical ResultPhase 3Phase 1

13 Jun 2024

·www.prnewswire.com

The American Diabetes Association Kicks Off the 84th Scientific Sessions with Breakthrough Diabetes Research

Leading Diabetes Scientific Sessions Meeting Will Present Groundbreaking Data on Key Topics Including: Obesity, Technology, AI Health and the Latest in Diabetes Innovation ORLANDO, Fla., June 13, 2024 /PRNewswire/ -- From June 21–24, the American Diabetes Association® (ADA) will host the 84th Scientific Sessions in Orlando, FL. The ADA's Scientific Sessions is the world's largest diabetes meeting, convening more than 11,000 leading physicians, scientists, researchers and health care professionals from around the globe. The hybrid meeting will feature the latest scientific findings in diabetes, including more than 200 sessions and 2,000 original research presentations at the Orange County Convention Center. Diabetes is among the top 10 leading causes of death in the United States, with more than 1.4 million new cases diagnosed each year. Over the past 20 years, the number of adults diagnosed with diabetes has more than doubled due to factors like increased obesity, weight gain and aging. During the annual meeting, the ADA is highlighting the latest cutting-edge advances in diabetes research and care. Among the key themes, you can expect: Obesity/weight-loss drugs: Obesity impacts 42% of American adults and contributes to up to 53% of the new cases of diabetes each year. This comes amid a surge of increased use of weight-loss drugs, with almost two million people in the U.S. taking semaglutide medications in 2021 —more than three times as many as in 2019. This year's meetings will feature several clinical studies addressing obesity treatment including groundbreaking data on glucagon-like peptide-1 (GLP-1) drugs and their impact on not only obesity and diabetes, but sleep apnea, kidney outcomes, and more. This will include data on Food and Drug Administration (FDA)-approved GLP-1 drugs such as Tirzepatide and a large number of GLP-1 drug candidates at various stages in the research pipeline, including Retatrutide, Pemvidutide and oral Ecnoglutide. Technology and AI: Innovative technologies and solutions are transforming diabetes management, offering new possibilities for improved patient outcomes and more personalized care. Studies will highlight advancements on solutions such as automated insulin delivery (AID) systems and new research on continuous glucose monitors (CGMs). Innovation: On Saturday, June 22 from 4:30-6:00 p.m. ET, the Innovation Challenge, which debuted in 2023, will once again invite emerging companies to pitch novel ideas to improve the lives of people living with diabetes. A panel of judges, with input from a live audience, determine which contestants will earn a private audience with potential funders. "As we commence the 84th Scientific Sessions, we are proud of our program that underscores our commitment to addressing the multifaceted challenges of diabetes," said Robert Gabbay, MD, PhD, the ADA's chief scientific and medical officer. "This year's program reflects our dedication to advancing research, fostering innovation, and ultimately improving the lives of those affected by diabetes. We look forward to an engaging and impactful event that will inspire and drive the future of diabetes care, at a pivotal time of pharmacological and technological advances in the field." Other notable topics and themes highlighted in the presentations at the 84th Scientific Sessions include eye health, health disparities, diabetes and obesity related cancers, and early risk monitoring. Most sessions, in addition to the 60-plus livestreamed sessions, will be available for on-demand viewing for attendees following the meeting through August 26. "This year's Scientific Sessions is set to highlight the latest and greatest advances in diabetes research with an exceptional, data-driven program," said Alice Y.Y. Cheng, MD, FRCPC, chair of the 84th Scientific Sessions Planning Committee. "Whether you're joining us in-person or virtually, you'll have the opportunity to engage with leading experts, participate in dynamic discussions, and gain valuable insights that will drive the future of diabetes care." Learn more about the 84th Scientific Sessions. For access to program navigation, educational session information, news updates, abstracts, and exhibitor information, the 2024 ADA Scientific Sessions mobile app and the online planner are your go-to meeting resources. For more information, please contact the ADA Scientific Sessions media at [email protected]. Embargo Policy: Oral presentations: Oral presentations are embargoed from the time of submission until the start of their presentation at the 84th Scientific Sessions. Symposiums (including late-breaking symposiums): Symposiums and presentations within symposiums are embargoed until the beginning of the Symposium session at the 84th Scientific Sessions. Poster presentations (including late-breaking posters): Poster presentations are embargoed from the time of submission until Friday, June 21, 2024, at 6:30 p.m. ET. About the American Diabetes Association's Scientific Sessions The ADA's 84th Scientific Sessions, the world's largest scientific meeting focused on diabetes research, prevention, and care, will be held in Orlando, FL on June 21-24. More than 11,000 leading physicians, scientists, and health care professionals from around the world are expected to convene both in person and virtually to unveil cutting-edge research, treatment recommendations, and advances toward a cure for diabetes. Attendees will receive exclusive access to thousands of original research presentations and take part in provocative and engaging exchanges with leading diabetes experts. Join the Scientific Sessions conversation on social media using #ADAScientificSessions. About the American Diabetes Association The American Diabetes Association (ADA) is the nation's leading voluntary health organization fighting to bend the curve on the diabetes epidemic and help people living with diabetes thrive. For 83 years, the ADA has driven discovery and research to treat, manage, and prevent diabetes while working relentlessly for a cure. Through advocacy, program development, and education we aim to improve the quality of life for the over 136 million Americans living with diabetes or prediabetes. Diabetes has brought us together. What we do next will make us Connected for Life®. To learn more or to get involved, visit us at diabetes.org or call 1-800-DIABETES (1-800-342-2383). Join the fight with us on Facebook (American Diabetes Association), Spanish Facebook (Asociación Americana de la Diabetes), LinkedIn (American Diabetes Association), Twitter (@AmDiabetesAssn), and Instagram (@AmDiabetesAssn). SOURCE American Diabetes Association

08 May 2024

·www.echemi.com

Breaking News: $56 Million Investment as GLP-1 Makes Its Way to South Korea

In a groundbreaking development, the biopharmaceutical company Sciwind Biosciences has announced a strategic partnership with HKinno.N Corporation, a leading pharmaceutical company in South Korea. The partnership involves the licensing and commercialization of Ecnoglutide Injection (XW003), a novel GLP-1 agonist, in the South Korean market. This collaboration marks a significant milestone in the expansion of GLP-1 therapies and is projected to be a game-changer in treating type 2 diabetes, obesity, and metabolic disorders such as non-alcoholic steatohepatitis (NASH). Partnership Details: According to the agreement, Sciwind Biosciences will receive an upfront payment and become eligible for milestone payments of up to $56 million for research, development, registration, and commercialization of Ecnoglutide Injection. Additionally, the company will receive a substantial royalty based on the product's sales in South Korea. HKinno.N Corporation, on the other hand, gains exclusive rights for the development and commercialization of Ecnoglutide Injection within the South Korean market. However, Sciwind Biosciences retains the rights to develop and commercialize the product in all other global markets. The Powerhouse Partnership: HKinno.N Corporation, formerly the pharmaceutical division of CJ CheilJedang Corp, has a rich history in the pharmaceutical industry. With over 16,000 international patents and more than 20,000 product formulations in skincare and medicine, the company boasts an impressive clientele and is considered a leading player in the consumer healthcare sector in South Korea. Leveraging their experience in successfully developing and commercializing K-CAB, a novel gastroesophageal reflux disease medication, HKinno.N Corporation aims to position Ecnoglutide Injection as a blockbuster drug with sales exceeding 100 billion Korean won in the South Korean market. The Potential of Ecnoglutide Injection: Ecnoglutide Injection is a newly developed GLP-1 agonist with a unique cyclic adenosine monophosphate (cAMP) bias. It demonstrates potential in treating type 2 diabetes, obesity, and metabolic disorders such as NASH. GLP-1 agonists have shown efficacy in managing type 2 diabetes and obesity by promoting insulin secretion and reducing appetite, with minimal risk of hypoglycemia. Ecnoglutide Injection, optimized for enhanced biological activity and cost-effectiveness, offers the convenience of once-weekly dosing. Clinical trials have shown promising results, with significant reductions in glycated hemoglobin (HbA1c) and body weight observed in patients. Future Prospects and Market Demand: Metabolic diseases affect millions of patients in South Korea, making the introduction of Ecnoglutide Injection a vital development. Dalwon Kwak, CEO of HKinno.N Corporation, expressed confidence in the product's clinical profile and differentiated features. Sciwind Biosciences's collaboration will accelerate the drug's research and development in the South Korean market. The demand for diabetes and weight management drugs is substantial, and GLP-1 receptor agonists have gained popularity due to their favorable effects on insulin secretion and appetite control, coupled with a low risk of side effects. Sciwind Biosciences, with its pioneering approach, has established a strong presence in this market. The strategic partnership between Sciwind Biosciences and HKinno.N Corporation brings the promising GLP-1 agonist, Ecnoglutide Injection, to the South Korean market. This alliance not only signifies a major investment of $56 million but also heralds a new era in the treatment of type 2 diabetes, obesity, and metabolic disorders. With the potential to revolutionize the healthcare landscape, Ecnoglutide Injection holds great promise for improving the lives of patients in South Korea and beyond.

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Indication	Highest Phase	Country/Location	Organization	Date
Obesity	Phase 3	CN	Hangzhou Sciwind Biosciences Co., Ltd.Startup	05 Apr 2023
Diabetes Mellitus, Type 2	Phase 3	CN	Hangzhou Sciwind Biosciences Co., Ltd.Startup	29 Dec 2022
Renal Insufficiency	Phase 1	CN	Hangzhou Sciwind Biosciences Co., Ltd.Startup	21 Aug 2023
Nonalcoholic Steatohepatitis	Phase 1	CN	Hangzhou Sciwind Biosciences Co., Ltd.Startup	16 Jun 2021
Alzheimer Disease	Preclinical	CN	Hangzhou Sciwind Biosciences Co., Ltd.Startup	19 May 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05680155 (ADA2024) Manual	Phase 3	Diabetes Mellitus, Type 2	211	Ecnoglutide 0.6 mg	viloofqgux(ldizmgockb) = upcgyifdgz cdxzyiwgeq (frzxdbvvky ) View more	Positive	21 Jun 2024
				Ecnoglutide 1.2 mg	viloofqgux(ldizmgockb) = qfhfnudubk cdxzyiwgeq (frzxdbvvky ) View more
NCT05184322 (ADA2024) Manual	Phase 1	Obesity	56	Oral Ecnoglutide 7mg (healthy)	tzmwmucmyq(cptvmpdbcn) = The most common AEs were mild to moderate gastrointestinal events that occurred during dose escalation. lqhdacilbz (zbwcahkbsm ) View more	Positive	21 Jun 2024
				Oral Ecnoglutide 15mg (healthy)
NEWS Manual	Phase 1	Obesity	56	ecnoglutide	qdmihombyd(pmrmmyczog) = 最常见的不良事件包括恶心、头痛、腹泻、呕吐和食欲减退，大多数不良事件的严重程度为轻中度，主要发生在剂量递增期 lrwsxgfeui (nrwezmqfoj )	Positive	24 Jan 2024
				placebo
NCT05680155 (NEWS) Manual	Phase 3	Diabetes Mellitus, Type 2	211	Ecnoglutide 0.6 mg	xdukgczulb(xjzjjeipea) = ahcrbaeaea rjfnidgiqw (jajxbazcgx ) View more	Positive	03 Jan 2024
				Ecnoglutide 1.2 mg	xdukgczulb(xjzjjeipea) = eqbdsrpevn rjfnidgiqw (jajxbazcgx ) View more
CTR20211014 (ADA2023) Manual	Phase 2	Diabetes Mellitus, Type 2	145	XW003 0.4 mg	qteauwmwcf(oqypzlfsnk) = kbehohqkbu xluoufkvpf (wemalkpuxz ) View more	Positive	20 Jun 2023
				XW003 0.8 mg	qteauwmwcf(oqypzlfsnk) = ytoupodvfm xluoufkvpf (wemalkpuxz ) View more
CTR20213434 (ADA2023) Manual	Phase 1	Overweight \| Obesity	60	XW003 1.8 mg	pnnsejvzpd(yrzntntgmn) = The proportion of participants reporting any AE was similar between cohorts (95.2 to 100% for ecnoglutide vs 90% for placebo). The most frequent AEs were gastrointestinal, including diarrhea and vomiting. No drug-related SAE or drug-related AEs ≥Grade 3 were reported. lcgrelkvkl (vjtfxhwmhx ) View more	Positive	20 Jun 2023
				XW003 2.4 mg
NCT05111912 (ADA2023) Manual	Phase 2	Obesity	206	XW003 1.2 mg	jkxnonvhnv(fdfwtxjzls) = itnipzzbgg vkcbeyndod (vbjcbtqofg )	Positive	20 Jun 2023
				XW003 1.8 mg	jkxnonvhnv(fdfwtxjzls) = ixwnptjuzx vkcbeyndod (vbjcbtqofg )

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