berberine ursodeoxycholate (HTD1801) / HighTide Therap - LARVOL DELTA

HTD1801 Demonstrates Promising Potential for Histologic Improvements in MASH in Both a Preclinical and Phase 2 Study. (PubMed, Clin Mol Hepatol) - "Dose-dependent improvements were observed across biomarkers, with more HTD1801-treated patients achieving response criteria associated with improvements in the histologic features of MASH. These findings suggest that HTD1801 has strong potential to produce histological improvements in patients with MASH."

Journal • P2 data • Preclinical • Addiction (Opioid and Alcohol) • Diabetes • Dyslipidemia • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Effects of Berberine Ursodeoxcholate (HTD1801) in chinese patients with T2DM and presumed MASLD (EASL 2025) - P2 | "HTD1801 treatment has demonstrated both cardiometabolic and hepatic benefits in Chinese patients with T2DM and presumed MASLD with dose dependent improvements in HbA1c, GGT and LDL-C. These data suggest HTD1801 can comprehensively address metabolic and cardiovascular risk factors beyond glycemic control. Further evaluation of HTD1801 continues in 3 Phase 3 studies of T2DM and a Phase 2b study of patients with MASH and T2DM/pre-diabetes."

Clinical • Cardiovascular • Dyslipidemia • Genetic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Effects of Berberine Ursodeoxcholate (HTD1801) in patients with at-risk MASH and T2DM (EASL 2025) - P2 | "Eighteen weeks of treatment with HTD1801 resulted in substantial improvements in key hepatic and cardiometabolic parameters in patients with probable at-risk MASH and twice as many patients achieved a reduction in LFC or fibroinflammation that have been associated with improvements in liver histology. These data are particularly insightful as HTD1801 continues to be evaluated in an ongoing paired biopsy study of patients with at-risk MASH and pre-diabetes or diabetes."

Clinical • Fibrosis • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

Berberine Ursodeoxycholate for the Treatment of Type 2 Diabetes: A Randomized Clinical Trial. (PubMed, JAMA Netw Open) - P2 | "The effects demonstrated by HTD1801 support an oral treatment option for T2D and its comorbidities. ClinicalTrials.gov Identifier: NCT06411275."

Clinical • Journal • Diabetes • Hematological Disorders • Hepatology • Liver Failure • Metabolic Disorders • Retinal Disorders • Type 2 Diabetes Mellitus

Effects of Berberine Ursodeoxycholate (HTD1801) Versus Dapagliflozin in Patients with Type 2 Diabetes Inadequately Controlled with Metformin (clinicaltrials.gov) - P3 | N=418 | Active, not recruiting | Sponsor: HighTide Biopharma Pty Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

EVALUATION OF EFFICACY OF BERBERINE URSODEOXYCHOLATE (HTD1801) COMPARED TO ONGOING USE OF GLP-1 RECEPTOR AGONISTS IN PATIENTS WITH MASH AND T2DM (AASLD 2024) - P2 | "This data suggests newly initiated HTD1801 provides greater benefit than ongoing GLP-1RA use. Utilization of GLP-1RA continues to grow and may be confounding in studies of MASH. This has resulted in their exclusion from some new studies of MASH which is unlikely to be reflective of real-world use."

Clinical • Genetic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • Type 2 Diabetes Mellitus

SCREENING AND COMPARISON OF CURRENT CLINICAL CANDIDATES IN MASH USING HUMAN LIVER SPHEROIDS (AASLD 2024) - "We show that the HTD1801 (berberine ursodeoxycholate, an ionic salt of berberine and ursodeoxycholic acid) reduces significantly the secretion of PC-1. We show for the first time a screening platform that combines toxicity and MASH efficacy readouts. We show the translational capacity of this platform of several clinical candidates by predicting clinical outcomes."

Clinical • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

TIME COURSE OF ONSET, INCIDENCE AND PREVALENCE OF GASTROINTESTINAL ADVERSE EVENTS WITH HTD1801 (BERBERINE URSODEOXYCHOLATE) IN PATIENTS WITH MASH AND T2DM (AASLD 2024) - P2 | "Background: HTD1801 is a gut-liver anti-inflammatory metabolic modulator consisting of an ionic salt combination including berberine and ursodeoxycholic acid. HTD1801 was found to be generally safe and well tolerated in this study. Although most commonly occurring AEs in studies involving HTD1801 are GI related and are typically mild to moderate in severity with decreasing incidence over time. The above data indicates subject tolerability to HTD1801 which improves over the course of treatment."

Adverse events • Clinical • Diabetes • Gastrointestinal Disorder • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Evaluate the Efficacy and Safety of HTD1801 in Patients with Type 2 Diabetes Mellitus (T2DM) (ChiCTR) - P2 | N=113 | Completed | Sponsor: Peking University People 's Hospital; Shenzhen HighTide Biopharmaceutical Ltd.

New P2 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • CRP

Efficacy of berberine ursodeoxycholate (HTD1801) in Chinese and Western patients with type 2 diabetes (EASD 2024) - P2 | "While the two populations are evidently ethnically distinct with a varied medical history, improvements in key measures of glycemic and cardiometabolic benefit with HTD1801 treatment were observed in both populations. These data further support the development of HTD1801 in T2DM and MASH."

Clinical • Diabetes • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

Berberine ursodeoxycholate (HTD1801) provides a unique therapeutic approach for patients with metabolic diseases and severe insulin resistance (EASD 2024) - "These data, while limited to a small number of subjects, suggest that HTD1801 can alleviate the metabolic inhibitory effects caused by hyperinsulinemia, leading to greater metabolic benefits and therefore may offer a unique therapeutic approach for individuals with metabolic diseases and elevated insulin levels. HTD1801 continues to be evaluated in the ongoing Phase 2b study in patients with NASH and T2DM."

Clinical • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

Efficacy and Safety of Berberine Ursodeoxycholate (HTD1801) in Patients With Type 2 Diabetes Inadequately Controlled With Metformin (clinicaltrials.gov) - P3 | N=551 | Active, not recruiting | Sponsor: HighTide Biopharma Pty Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Safety of Berberine Ursodeoxycholate (HTD1801) in Patients With Type 2 Diabetes (clinicaltrials.gov) - P3 | N=408 | Active, not recruiting | Sponsor: HighTide Biopharma Pty Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Berberine Ursodeoxycholate (HTD1801) Improves Key Glycemic and Cardiometabolic Parameters across the Type 2 Diabetes Mellitus Disease Spectrum (ADA 2024) - "Regardless of BL disease severity, HTD1801 treatment resulted in significant improvements in key glycemic and cardiometabolic parameters. HTD1801 continues to be evaluated for T2DM in Ph3 studies."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Time course of onset, incidence and prevalence of gastrointestinal adverse events with HTD1801 (Berberine Ursodeoxycholate) in patients with MASH and T2DM (EASL-ILC 2024) - P2 | "Background and Aims: HTD1801 is a gut-liver anti-inflammatory metabolic modulator consisting of an ionic salt combination including berberine and ursodeoxycholic acid. HTD1801 was found to be generally safe and well tolerated in this study. Although most commonly occurring AEs in studies involving HTD1801 are GI related, these events are typically mild to moderate in severity with decreasing incidence over time. Furthermore, these data indicate that tolerability to HTD1801 improves over the course of treatment."

Adverse events • Clinical • Gastrointestinal Disorder • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

Evaluation of efficacy of Berberine Ursodeoxycholate (HTD1801) compared to ongoing use of GLP-1 receptor agonists in patients with MASH and T2DM (EASL-ILC 2024) - P2 | "This data suggests newly initiated HTD1801 provides greater benefit than ongoing GLP-1RA use. Utilization of GLP-1RA continues to grow and may be confounding in studies of MASH. This has resulted in their exclusion from some new studies of MASH which is unlikely to be reflective of real-world use."

Clinical • Genetic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • Type 2 Diabetes Mellitus

Berberine Ursodeoxycholate (HTD1801) provides a unique therapeutic approach for patients with metabolic diseases and severe insulin resistance (EASL-ILC 2024) - "These data, while limited to a small number of subjects, suggest that HTD1801 can alleviate the metabolic inhibitory effects caused by hyperinsulinemia, leading to greater metabolic benefits and therefore may offer a unique therapeutic approach for individuals with metabolic diseases and elevated insulin levels. HTD1801 continues to be evaluated in the ongoing Phase 2b study in patients with MASH and T2DM."

Clinical • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

Effects of Berberine Ursodeoxycholate (HTD1801) Versus Dapagliflozin in Patients With Type 2 Diabetes Inadequately Controlled With Metformin (clinicaltrials.gov) - P3 | N=418 | Recruiting | Sponsor: HighTide Biopharma Pty Ltd

New P3 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

A Phase 2 Study of Berberine Ursodeoxycholate (HTD1801) in Patients With Type 2 Diabetes Inadequately Controlled With Diet and Exercise (clinicaltrials.gov) - P2 | N=113 | Completed | Sponsor: HighTide Biopharma Pty Ltd

New P2 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

HTD1801 in Patients With Type 2 Diabetes Mellitus Who Have Poor Glycemic Control After Metformin Treatment (clinicaltrials.gov) - P3 | N=555 | Recruiting | Sponsor: HighTide Biopharma Pty Ltd

New P3 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

HTD1801 in Patients With Type 2 Diabetes Mellitus Who Have Poor Glycemic Control After Dietary and Exercise Interventions (clinicaltrials.gov) - P3 | N=405 | Recruiting | Sponsor: HighTide Biopharma Pty Ltd

New P3 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

CENTRICITY: HTD1801 in Adults With Nonalcoholic Steatohepatitis and Liver Fibrosis Who Have Type 2 Diabetes or Pre-Diabetes (clinicaltrials.gov) - P2 | N=218 | Active, not recruiting | Sponsor: HighTide Biopharma Pty Ltd | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ May 2025 | Trial primary completion date: Dec 2024 ➔ Mar 2025

Enrollment closed • Trial completion date • Trial primary completion date • Diabetes • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

CENTRICITY: HTD1801 in Adults With Nonalcoholic Steatohepatitis and Liver Fibrosis Who Have Type 2 Diabetes or Pre-Diabetes (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: HighTide Biopharma Pty Ltd | Phase classification: P2b ➔ P2

Phase classification • Diabetes • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

NASH (AASLD 2023) - P2, P2b | "Twice as many patients achieved MRI response criteria with HTD1801 compared to placebo. Furthermore, improvements were observed with HTD1801 in liver biochemistry and key cardiometabolic parameters in both responders and non-responders. HTD1801 continues to be evaluated in a biopsy-based Phase 2b study (NCT05623189)."

Diabetes • Hepatology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Type 2 Diabetes Mellitus

HTD1801 improves glycaemic control in patients with type 2 diabetes: double-blind, placebo-controlled, phase 2 study (EASD 2023) - "The primary endpoint was achieved with a significant reduction in HbA1c after 12 weeks of treatment with HTD1801 and additional improvements in key cardiometabolic parameters. HTD1801 was found to be generally safe and well tolerated. These findings will be further evaluated in Phase 3 studies in patients with T2DM."

Clinical • P2 data • Diabetes • Hypoglycemia • Metabolic Disorders • Non-alcoholic Steatohepatitis • Type 2 Diabetes Mellitus