Tag: HighTide Therapeutics Inc.

HighTide Therapeutics, Inc. (HKG: 2511), a clinical stage biopharmaceutical company specializing in the development of multifunctional multi-targeted therapies for chronic liver and metabolic diseases, announced today that it will present at the EASL Congress 2025, taking place from May 7-10, 2025 in Amsterdam. The presentations include post-hoc analyses of two Phase 2 clinical studies of berberine ursodeoxycholate (HTD1801), a gut-liver anti-inflammatory metabolic modulator, being developed for treatment of metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes mellitus (T2DM). A third presentation will present preclinical results for rimtoregtide (HTD4010), a peptide derived from the Reg3a protein, in liver failure in mice.

“Effects of Berberine Ursodeoxycholate (HTD1801) in Patients with At-risk MASH and T2DM”
(Presentation SAT-440, Poster Presentation, May 10, 8:30 AM CET)

About the Abstract: Due to the ongoing unmet medical need, clinical development in MASH focuses on patients who are at a higher risk of disease progression and outcomes due to the presence of moderate to advanced fibrosis (defined as at-risk MASH). The purpose of this analysis was to assess the effects of HTD1801 in patients with at-risk MASH and T2DM as defined by baseline MRI cT1 >875 ms. Eighteen weeks of treatment with HTD1801 resulted in substantial improvements in key hepatic and cardiometabolic parameters in patients with at-risk MASH and compared to placebo, twice as many patients achieved a reduction in liver fat content (MRI-PDFF) or fibroinflammation (cT1) 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.

“Effects of Berberine Ursodeoxycholate (HTD1801) in Chinese Patients with T2DM and Presumed MASLD”
(Presentation SAT-432, Poster Presentation, May 10, 8:30 AM CET)

About the Abstract: T2DM typically coexists with other metabolic abnormalities such as hyperlipidemia, obesity, and MASH that can exacerbate T2DM and can lead to a worse prognosis with increased risk for mortality and cardiovascular outcomes. In a Phase 2 study in patients with T2DM, HTD1801 achieved the primary endpoint with a significant decrease in HbA1c. Based on the latest diagnostic criteria, it is likely that a substantial subgroup of the study may have had concurrent metabolic dysfunction-associated steatotic liver disease (MASLD). The purpose of this analysis was to evaluate the benefits of HTD1801 in patients with T2DM and MASLD identified by baseline controlled attenuation parameter values >288 dB/M (correlated to 5% liver fat content). HTD1801 treatment demonstrated both dose-dependent improvements in cardiometabolic and hepatic parameters in patients with T2DM and MASLD. These data suggest HTD1801 can comprehensively address metabolic and cardiovascular risk factors beyond glycemic control.

“A Comparison of the Protective Effects of Rimtoregtide (HTD4010) and DUR-928 on Acute Liver Failure in Mice”
(Presentation FRI-141, Poster Presentation, May 9, 8:30 AM CET)

About the Abstract: The purpose of this study was 1) to test the potential protective effects of HTD4010 in an LPS-induced model mimicking acute liver failure in mice and 2) compare these effects to DUR-928, which is currently in late-stage development for the treatment of alcohol-associated hepatitis. In an LPS-induced mouse model mimicking acute liver failure, HTD4010 resulted in significant improvement in survival rates (greater than 2-fold) compared to the model control.  These protective effects of HTD4010 were significantly greater than DUR-928.  These findings provide evidence that HTD4010 may have a beneficial effect on acute liver conditions including alcohol-associated hepatitis and other acute-inflammatory-related conditions.

About Berberine Ursodeoxycholate
Berberine ursodeoxycholate (HTD1801) is an orally delivered, gut-liver anti-inflammatory metabolic modulator being developed for the treatment of metabolic and digestive diseases. HTD1801, an ionic salt of berberine and ursodeoxycholate, is a new molecular entity with a unique dual mechanism of action: AMP kinase activation and NLRP3 inflammasome inhibition. These two key mechanistic pathways have been associated with improvements in insulin resistance, glucose metabolism, lipid metabolism, and hepatic inflammation, potentially providing a comprehensive treatment platform for the multifaceted nature of complex metabolic diseases. HTD1801 is being developed for multiple indications. HTD1801 met the primary endpoint in two Phase 3 clinical trials in patients with type 2 diabetes mellitus (T2DM), demonstrating a clinically meaningful effect on HbA1c. In both trials, key secondary endpoints were achieved, suggesting multiple advantages of HTD1801 including improvement in cardiometabolic risk indicators. In addition to T2DM, HTD1801 efficacy in treating metabolic dysfunction-associated steatohepatitis (MASH) has been demonstrated in a Phase 2a clinical trial, and a global multicenter Phase 2b trial assessing the histologic benefit of HTD1801 is currently ongoing, with topline results expected in 2025.

About Rimtoregtide
Rimtoregtide (HTD4010) is a clinical-stage compound in development for acute inflammatory-related indications including alcoholic hepatitis (AH). It is a peptide derived from the Reg3a protein with immunomodulatory, anti-inflammatory, and anti-apoptotic effects. HTD4010 has been evaluated in animal models of acute pancreatitis and acute liver failure, where protective effects were observed. A completed Phase 1 clinical trial of HTD4010 in healthy subjects demonstrated a favorable safety profile. AH is caused by chronic heavy alcohol abuse or a sudden, drastic increase in alcohol consumption. It is characterized by severe inflammation and, ultimately, liver failure and death. There is currently no approved treatment for AH and only a few drug candidates are in clinical development. The current standard of care focuses on symptom management, including abstinence, treating inflammation and providing nutrition.

About HighTide Therapeutics
HighTide Therapeutics, Inc. (HKG: 2511) is a globally integrated biopharmaceutical company focusing on the discovery and development of first-in-class multifunctional, multi-targeted therapies with poly-indication potential across metabolic diseases with significant unmet medical needs. HighTide is currently developing several clinical assets and associated global intellectual property rights, and advancing multiple mid-to-late-stage clinical trials including therapies for metabolic dysfunction-associated steatohepatitis (MASH), type 2 diabetes mellitus (T2DM), severe hypertriglyceridemia (SHTG) and primary sclerosing cholangitis (PSC). Berberine ursodeoxycholate (HTD1801), HighTide’s lead drug candidate, received Fast Track designation from the United States Food and Drug Administration for both MASH and PSC and Orphan Drug designation for PSC. HTD1801 has been included in the National Major New Drug Innovation Program under the 13th Five-Year Plan for Major Technology Project in China.

For more information, please visit www.hightidetx.com
Contact: pr@hightidetx.com

• HighTide Therapeutics Announces HTD1801 Meets the Primary Endpoints in Two Phase 3 Clinical Trials in Patients with Type 2 Diabetes Mellitus

HighTide Therapeutics, Inc. (HKG: 2511), a clinical-stage biopharmaceutical company specializing in the development of multifunctional, multi-targeted therapies for chronic liver and metabolic diseases, today announced that two Phase 3 trials (SYMPHONY 1 and SYMPHONY 2) of berberine ursodeoxycholate (HTD1801) in Chinese patients with type 2 diabetes mellitus (T2DM) met their primary endpoints and gated secondary endpoints.

The results of these two Phase 3 clinical trials provide robust evidence that HTD1801 delivers comprehensive benefits for patients with T2DM. Based on these highly positive read-outs, HighTide plans to submit a new drug application (NDA) for HTD1801 as a treatment for T2DM to the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) later this year.

SYMPHONY 1 (NCT06350890) and SYMPHONY 2 (NCT06353347) are randomized, double-blind, placebo-controlled, Phase 3 clinical trials designed to evaluate the efficacy and safety of HTD1801 in adults with T2DM and inadequate glycemic control despite using diet and exercise (SYMPHONY 1; N=407) or Metformin (SYMPHONY 2; N=549). The primary endpoint in both studies was the change in HbA1c from baseline with HTD1801 compared to placebo after 24 weeks of treatment. Gated secondary endpoints included the percentage of subjects achieving HbA1c <7.0%, change in fasting plasma glucose (FPG), low-density lipoprotein cholesterol (LDL-C), glutamyl transpeptidase (GGT), and high-sensitivity C-reactive protein (hs-CRP).

The primary endpoint was achieved in both trials, showing a clinically meaningful, consistent glucose-lowering effect of HTD1801
SYMPHONY 1 (HTD1801 as monotherapy): At week 24, the reduction from baseline in HbA1c with HTD1801 (-1.3%) was superior to placebo. Further, those with more severe disease had a greater decrease with HTD1801: reduction in HbA1c was -1.5% for those with a baseline HbA1c ≥8.5%.

SYMPHONY 2 (HTD1801 as an add-on therapy to Metformin): At week 24, the reduction from baseline in HbA1c with HTD1801 (-1.2%) was superior to placebo. Further, those with more severe disease had a more significant decrease with HTD1801: reduction in HbA1c was -1.6% for those with a baseline HbA1c ≥8.5%.

In both Phase 3 trials, the efficacy on HbA1c reduction in patients treated with HTD1801 was sustained through week 24.

In both trials, gated secondary endpoints were achieved, suggesting multiple advantages of HTD1801 beyond glucose-lowering including improvement in cardiometabolic risk indicators
At week 24, in both studies, the proportion of patients who achieved HbA1c <7.0% was significantly higher in the HTD1801 treatment groups compared to placebo. Improvements in HbA1c with HTD1801 were parallelled with significant improvements in postprandial and fasting plasma glucose compared with placebo. In addition, HTD1801 demonstrated lipid-lowering effects, including significant reductions in low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). Moreover, HTD1801 treatment led to reductions in key inflammatory biomarkers – glutamyl transpeptidase (GGT) and high-sensitivity C-reactive protein (hs-CRP) – both of which are associated with cardiovascular risk in patients with T2DM.

Favorable safety and tolerability profile
Overall, safety and tolerability were favorable and consistent with previous clinical trials of HTD1801. The most commonly reported adverse events were gastrointestinal. In both studies <2% of patients discontinued early due to an adverse event. The incidence of hypoglycemia was low, with no severe hypoglycemia events reported.

“The encouraging results from these studies suggest that HTD1801 may offer a novel and improved therapeutic option for patients with T2DM,” said Dr. Linong Ji, the leading principal investigator for the two Phase 3 clinical trials and former Vice President of the International Diabetes Federation (IDF), Director of the Peking University Diabetes Center and Director of the Department of Endocrinology and Metabolism, Peking University People’s Hospital. “As an innovative drug candidate, HTD1801 exhibits a unique dual mechanism of action – AMP kinase activation and NLRP3 inflammasome inhibition – that is distinct from any existing T2DM drugs on the market. It is an oral therapy designed to deliver comprehensive clinical benefits – not only lowering blood glucose but also improving lipid metabolism and exerting anti-inflammatory effects – thereby potentially reducing diabetes-related complications and addressing significant unmet clinical needs. With continued clinical exploration, HTD1801 is expected to further expand its application to benefit patients globally. In today’s pharmaceutical landscape, investment has become heavily concentrated on GLP-1-based drug development. While GLP-1 therapies hold significant clinical value, they do not adequately address the full spectrum of pathophysiological mechanisms underlying T2DM. To truly meet the multifaceted needs of T2DM management, continued innovation across a diverse range of therapeutic targets remains essential.”

“We extend our deepest gratitude to the patients who participated in these pivotal trials,” said Dr. Liping Liu, HighTide’s founder and CEO. “HTD1801’s innovative dual-action approach – targeting both metabolic regulation and inhibiting inflammation – represents a potential breakthrough in diabetes treatment. We look forward to sharing data from the 28-week open-label extension of these studies and a Phase 3 head-to-head comparison with the dapagliflozin; we will continue to explore the clinical potential of HTD1801 to provide patients with chronic metabolic diseases a comprehensive treatment solution.”

About Type 2 Diabetes Mellitus (T2DM)
According to the International Diabetes Federation (IDF), 537 million adults (ages 20-79) were living with diabetes in 2021, and this number is projected to grow to 783 million (representing 1 in 8 adults) by 2045, of these, around 90% are T2DM cases. China has the largest population of diabetes patients worldwide, estimated to be 141 million in 2021, and projected to grow to 174 million in 2045. Diabetes is a global societal burden leading to over 6 million deaths per year. To address this urgent challenge, there is a critical need for innovative therapies that can deliver comprehensive clinical benefits for patients worldwide.

About Berberine Ursodeoxycholate (HTD1801)
Berberine ursodeoxycholate (HTD1801) is an orally delivered, gut-liver anti-inflammatory metabolic modulator being developed for the treatment of metabolic and digestive diseases. HTD1801, an ionic salt of berberine and ursodeoxycholate, is a new molecular entity with a unique dual mechanism of action: AMP kinase activation and NLRP3 inflammasome inhibition. These two key mechanistic pathways have been associated with improvements in insulin resistance, glucose metabolism, lipid metabolism, and hepatic inflammation, potentially providing a comprehensive treatment platform for the multifaceted nature of complex metabolic diseases.

HTD1801 is being developed for multiple indications. In addition to T2DM, its efficacy in treating metabolic dysfunction-associated steatohepatitis (MASH) has been demonstrated in a Phase 2a clinical trial and a global multicenter Phase 2b trial assessing the histologic benefit of HTD1801 is currently ongoing, with topline results expected in 2025.

About HighTide Therapeutics
HighTide Therapeutics, Inc. (HKG: 2511) is a globally integrated biopharmaceutical company focusing on the discovery and development of first-in-class multifunctional, multi-targeted therapies with poly-indication potential across chronic liver and metabolic diseases with significant unmet medical needs. HighTide is currently developing several clinical assets and associated global intellectual property rights, and advancing multiple mid-to-late-stage clinical trials including therapies for metabolic dysfunction-associated steatohepatitis (MASH), type 2 diabetes mellitus (T2DM), severe hypertriglyceridemia (SHTG) and primary sclerosing cholangitis (PSC). Berberine ursodeoxycholate (HTD1801), HighTide’s lead drug candidate, received Fast Track designation from the United States Food and Drug Administration for both MASH and PSC and Orphan Drug designation for PSC. HTD1801 has been included in the National Major New Drug Innovation Program under the 13th Five-Year Plan for Major Technology Project in China.

For more information, please visit www.hightidetx.com.
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– Data from the proof-of-concept study showed berberine ursodeoxycholate was generally well tolerated and had beneficial therapeutic effect in improving glycemic, hepatic and cardiometabolic parameters
– The multifaceted effects demonstrated by berberine ursodeoxycholate support this new molecular entity as a unique oral treatment option for T2DM and its comorbidities
– T2DM phase 3 data readout is expected to be announced in the first half of 2025

HighTide Therapeutics, Inc. (HKG: 2511), a clinical stage biopharmaceutical company specializing in the development of multifunctional multi-targeted therapies for chronic liver and metabolic diseases, today announced that data from the Phase 2 proof-of-concept study evaluating berberine ursodeoxycholate (HTD1801) for the treatment of type 2 diabetes mellitus (T2DM) was published online in JAMA Network Open. 

The publication reports results of the randomized, placebo-controlled 12-week study to assess efficacy, safety and tolerability of HTD1801 compared to placebo in patients with T2DM. The trial achieved its primary endpoint by demonstrating a statistically significant and superior reduction in HbA1c at week 12 with HTD1801 versus placebo. A majority of patients treated with HTD1801 achieved target HbA1c <7%. Further, results show therapeutic benefit of HTD1801 on LDL and total cholesterol, markers of liver injury and systemic inflammation. In this study, HTD1801 was well tolerated with no treatment-related serious adverse events observed. These findings are being confirmed in ongoing Phase 3 studies.

“We are encouraged by the results of this Phase 2 study. The study provides evidence that HTD1801 can treat the core aspects of metabolic syndrome, with potential to provide a spectrum of therapeutic effects that appear to address comorbid conditions that exacerbate disease and worsen prognosis of patients with T2DM,” said Dr. Linong Ji, Professor of Medicine at Peking University, Director of Peking University Diabetes Center and Director of the Department of Endocrinology and Metabolism, Peking University People’s Hospital, in Beijing, China.

“Based on these positive findings, we are continuing to advance the clinical development of HTD1801 in our ongoing Phase 3 T2DM program with topline results expected in the first half of this year,” said Dr. Liping Liu, CEO of HighTide Therapeutics.

About JAMA Network Open Journal
JAMA Network Open is an international, peer-reviewed, open access, general medical journal that publishes research on clinical care, innovation in health care, health policy, and global health across all health disciplines and countries for clinicians, investigators, and policy makers. JAMA Network Open is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications.

About Berberine Ursodeoxycholate (HTD1801)
Berberine ursodeoxycholate (HTD1801) is an orally delivered, gut-liver anti-inflammatory metabolic modulator being developed for the treatment of metabolic and digestive diseases. HTD1801, an ionic salt of berberine and ursodeoxycholate, is a new molecular entity with unique dual mechanisms of action, including AMP kinase activation and NLRP3 inflammasome inhibition. These two key mechanistic pathways have been associated with improvements in glucose metabolism, insulin resistance, lipid metabolism, and hepatic inflammation, potentially providing a comprehensive treatment platform for the multifaceted nature of complex metabolic diseases such as T2DM.

About HighTide Therapeutics
HighTide Therapeutics, Inc. (HKG: 2511) is a globally integrated biopharmaceutical company focusing on the discovery and development of first-in-class multifunctional multi-targeted therapies with poly-indication potential across multiple metabolic and digestive diseases with significant unmet medical needs. The Company is currently developing several clinical assets and holding global intellectual property rights, advancing multiple mid-to-late-stage clinical trials including therapy for metabolic dysfunction-associated steatohepatitis (MASH), type 2 diabetes mellitus (T2DM), severe hypertriglyceridemia (SHTG) and primary sclerosing cholangitis (PSC). Berberine ursodeoxycholate (HTD1801), the Company’s lead drug candidate, received Fast Track designation from the United States Food and Drug Administration for both MASH and PSC and Orphan Drug designation for PSC. HTD1801 has been included in the National Major New Drug Innovation Program under the 13th Five-Year Plan for Major Technology Project in China.

For more information, please visit www.hightidetx.com. 

Contact: pr@hightidetx.com

Highlighting Benefits of Berberine Ursodeoxycholate (HTD1801)

HighTide Therapeutics, Inc. (HKG: 2511), a clinical stage biopharmaceutical company specializing in the development of multifunctional multi-targeted therapies for chronic liver and metabolic diseases, presents at the 60th European Association for the Study of Diabetes (EASD) Annual Meeting, taking place from September 10-13, 2024 in Madrid, Spain. The presentations include post-hoc analyses of two Phase 2 clinical studies of berberine ursodeoxycholate (HTD1801), a gut-liver anti-inflammatory metabolic modulator, in patients with type 2 diabetes mellitus (T2DM).

“These data provide additional insight on the potential benefits of HTD1801, a novel, multifunctional therapy being developed for the treatment of patients with T2DM. The two ongoing Phase 3 studies (NCT06350890, NCT06415773), fully enrolled in 2Q 2024, evaluate the efficacy and safety of HTD1801 in T2DM patients (as monotherapy or in combination with metformin). We look forward to the results of these Phase 3 studies which we expect to announce in 2025,” said Dr. Leigh MacConell, Chief Development Officer of HighTide.

“Efficacy of Berberine Ursodeoxycholate (HTD1801) in Chinese and Western Patients with T2DM”
(Presentation 711, Oral Presentation, September 11, 12:45 PM CEST)

About the Abstract: T2DM and MASH are highly interrelated, the presence of each increasing risk of outcomes. Patients with both T2DM and MASH are at higher risk of histologic progression in MASH, cardiovascular outcomes, hepatic outcomes, and all-cause mortality. The purpose of this analysis was to compare the effects of HTD1801 in Chinese and Western patients with T2DM with or without MASH. These data demonstrate that while the two populations are ethnically distinct with related but different diseases, treatment with HTD1801 was associated with improvements in key measures of glycemic, cardiometabolic, and hepatic benefit in both populations. HTD1801 offers holistic benefits that are observed in both Chinese and Western patients, irrespective of underlying disease, that address core aspects of both T2DM and MASH.

“Berberine Ursodeoxycholate (HTD1801) Provides a Unique Therapeutic Approach for Patients with Metabolic Diseases and Severe Insulin Resistance”

(Presentation 708, Oral Presentation, September 11, 12:45 PM CEST)

About the Abstract: Insulin resistance is a significant risk factor for T2DM, obesity and MASH. HTD1801 enhances the utilization of glucose and fats through activation of AMP-activated protein kinase (AMPK), thereby improving insulin sensitivity. As HTD1801 is under development as a treatment for patients with T2DM, as well as MASH, we analyzed the effects of HTD1801 response based on degree of insulin resistance. These data demonstrate that HTD1801 can alleviate the metabolic inhibitory effects caused by hyperinsulinemia, leading to even greater hepatic and metabolic benefits in patients with more severe insulin resistance, offering a unique therapeutic approach for individuals with T2DM and/or MASH.

About HighTide Therapeutics
HighTide Therapeutics, Inc. (HKG: 2511) is a globally integrated biopharmaceutical company focusing on the discovery and development of first-in-class multifunctional multi-targeted therapies with chronic liver and metabolic diseases with significant unmet medical needs. The company is developing multiple clinical assets, including therapy for metabolic dysfunction-associated steatohepatitis (MASH), type 2 diabetes (T2DM), severe hypertriglyceridemia (SHTG), primary sclerosing cholangitis (PSC). Berberine ursodeoxycholate (HTD1801), the company’s lead drug candidate, received Fast Track designation from the U.S. FDA for both NASH and PSC, as well as Orphan Drug designation for PSC. In China, HTD1801 has been included in the National Major New Drug Innovation Program under the 13th Five-Year Plan for Major Technology Project.

For more information, please visit www.hightidetx.com
Contact: pr@hightidetx.com

HighTide Therapeutics, Inc. (HKG: 2511), a clinical stage biopharmaceutical company specializing in the development of multi-targeted therapies for chronic liver and metabolic diseases, announced today that it will present at the American Diabetes Association’s (ADA) 84th Scientific Sessions, taking place from June 21-24, 2024 in Orlando, Florida. The presentation is a post-hoc analysis of the Phase 2 clinical study of berberine ursodeoxycholate (HTD1801), a gut-liver anti-inflammatory metabolic modulator, in patients with type 2 diabetes mellitus (T2DM) (NCT06411275).

Based on the successful Phase 2 study, two Phase 3 studies (NCT06350890, NCT06353347) are currently ongoing to further evaluate the efficacy and safety of HTD1801 (as monotherapy and as add-on to metformin) in patients with T2DM and inadequate control. “We look forward to the results of our pivotal T2DM program which we expect to announce in the first half of 2025,” said Dr. Leigh MacConell, Chief Development Officer of HighTide.

“Berberine Ursodeoxycholate (HTD1801) Improves Key Glycemic and Cardiometabolic Parameters Across the T2DM Disease Spectrum” (Abstract 847-P, Poster Presented June 23rd)
About the Abstract:
In a Phase 2, placebo-controlled, double-blind study in patients with T2DM, treatment with HTD1801 for 12 weeks resulted in significant dose-dependent improvements in key glycemic parameters. The objective of this post-hoc analysis was to evaluate the effectiveness of HTD1801 in patients with T2DM across the disease spectrum based on baseline HbA1c, with a particular emphasis on glycemic and lipid metabolism markers, along with indicators of liver injury. These data show that regardless of baseline disease severity, HTD1801 treatment resulted in significant improvements across these key parameters. The magnitude of improvement was greater in those with more severe disease. HTD1801 may offer a unique therapeutic approach for individuals with T2DM and other comorbidities (i.e. MASH and dyslipidemia), as managing these conditions effectively is crucial in controlling T2DM and reducing its associated complications.

About HighTide Therapeutics

HighTide Therapeutics, Inc. (2511.HK) is a globally integrated biopharmaceutical company focusing on the discovery and development of first-in-class multifunctional multi-targeted therapies with chronic liver and metabolic diseases with significant unmet medical needs. The company is developing multiple clinical assets, including therapy for metabolic dysfunction-associated steatohepatitis (MASH), type 2 diabetes (T2DM), severe hypertriglyceridemia (SHTG), primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Berberine ursodeoxycholate (HTD1801), the company’s lead drug candidate, received Fast Track designation from the U.S. FDA for both NASH and PSC, as well as Orphan Drug designation for PSC. In China, HTD1801 has been included in the National Major New Drug Innovation Program under the 13th Five-Year Plan for Major Technology Project.

Disclaimer
The information contained herein is based solely on events or data available as of the date of this document. Unless required by law, we are under no obligation to update or publicly revise any forward-looking statements or events beyond those anticipated, even if new information, future events, or other circumstances arise after the date of the forward-looking statement. Please review this document carefully and be aware that our actual future performance or results may significantly deviate from expectations. All statements in this document are made as of the publication date and may change considering future developments.

For more information, please visit www.hightidetx.com 
Contact: pr@hightidetx.com 

HighTide Therapeutics, Inc. (HKG: 2511), a clinical stage biopharmaceutical company specializing in the development of multi-targeted therapies for chronic liver and metabolic diseases, announced that it will make multiple presentations at the European Association for the Study of the Liver (EASL) Congress, taking place from June 5-8, 2024 in Milan, Italy. The presentations include post-hoc analyses of the Phase 2a clinical study of berberine ursodeoxcyholate (HTD1801), a gut-liver anti-inflammatory metabolic modulator, in patients with metabolic dysfunction-associated steatohepatitis (MASH) and comorbid type 2 diabetes mellitus (T2DM) (NCT03656744).

“These data provide additional insight on the potential benefits of HTD1801, a novel, multifunctional therapy being developed for the treatment of patients with MASH and T2DM. The ongoing multi-regional Phase 2b study (CENTRICITY, NCT05623189), now fully enrolled, evaluates the histologic benefit of HTD1801 in this same patient population. We look forward to the results of CENTRICITY which is on track to read out in the first half of 2025,” said Dr. Leigh MacConell, Chief Development Officer of HighTide.

“Efficacy of Berberine Ursodeoxycholate (HTD1801) Compared to Ongoing Use of GLP-1 Receptor Agonists in Patients with MASH and T2DM” (Abstract SAT-227, Poster Presented June 8)

About the Abstract: As GLP-1 Receptor Agonists (GLP-1RAs) are prominently used in patients with T2DM and gaining attention as a potential treatment for MASH, this post-hoc comparative efficacy analysis evaluated ongoing GLP-1RA use compared to newly initiated HTD1801 treatment. This analysis suggests that HTD1801 provides greater benefit across multiple cardiometabolic endpoints compared to ongoing GLP-1RA use. These findings are important as they suggest that patients with MASH and T2DM, on concomitant GLP-1RA treatment, could achieve additional benefit with HTD1801 in terms of further glucose and lipid lowering as well as weight loss.

“Berberine Ursodeoxycholate (HTD1801) Provides a Unique Therapeutic Approach for Patients with Metabolic Liver Disease and Severe Insulin Resistance” (Abstract SAT-225, Poster Presented June 8)

About the Abstract: Insulin resistance is a significant risk factor for T2DM, obesity and MASH. HTD1801 enhances the utilization of glucose and fats through activation of AMP-activated protein kinase (AMPK), thereby improving insulin sensitivity. As HTD1801 is under development as a treatment for patients with MASH and T2DM, the objective of this post-hoc analysis was to evaluate the effects of HTD1801 based on degree of insulin resistance. These data demonstrate that HTD1801 can alleviate the metabolic inhibitory effects caused by hyperinsulinemia, leading to even greater metabolic benefits in patients with MASH and more severe insulin resistance and therefore may offer a unique therapeutic approach for individuals with MASH and T2DM.

“Time Course of Onset, Incidence, and Prevalence of Gastrointestinal Adverse Events with HTD1801 (Berberine Ursodeoxycholate) in Patients with MASH and T2DM” (Abstract SAT-243, Poster Presented June 8)

About the Abstract: The most commonly occurring adverse events (AEs) in studies of HTD1801 across several indications have been mild to moderate gastrointestinal (GI) AEs, primarily diarrhea and nausea. The purpose of this post-hoc analysis was to characterize the time course and severity of GI AEs in patients with MASH and T2DM treated with HTD1801 for 18 weeks. Diarrhea and nausea, the most commonly occurring of GI AEs, followed a trend that was consistent with all reported GI AEs; they showed early onset (within the first 4 weeks), were mild or moderate in severity, and importantly, showed a decreasing incidence and prevalence over the course of treatment. These data demonstrate that with continued treatment with HTD1801, GI tolerability improves supporting its potential for long-term use for the treatment of chronic disease, such as MASH.

About HighTide Therapeutics

HighTide Therapeutics, Inc. (HKEX: 2511) is a globally integrated biopharmaceutical company focusing on the discovery and development of first-in-class multifunctional multi-targeted therapies with chronic liver and metabolic diseases with significant unmet medical needs. The company is developing multiple clinical assets, including therapy for metabolic dysfunction-associated steatohepatitis (MASH), type 2 diabetes (T2DM), severe hypertriglyceridemia (SHTG), primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Berberine ursodeoxycholate (HTD1801), the company’s lead drug candidate, received Fast Track designation from the U.S. FDA for both NASH and PSC, as well as Orphan Drug designation for PSC. In China, HTD1801 has been included in the National Major New Drug Innovation Program under the 13th Five-Year Plan for Major Technology Project.

Disclaimer
The information contained herein is based solely on events or data available as of the date of this document. Unless required by law, we are under no obligation to update or publicly revise any forward-looking statements or events beyond those anticipated, even if new information, future events, or other circumstances arise after the date of the forward-looking statement. Please review this document carefully and be aware that our actual future performance or results may significantly deviate from expectations. All statements in this document are made as of the publication date and may change considering future developments.

For more information, please visit www.hightidetx.com.

Contact: pr@hightidetx.com 

HighTide Therapeutics Inc. (HighTide), a globally integrated clinical-stage biopharmaceutical company developing novel multifunctional therapies for metabolic and digestive diseases, today announced the dosing of the first patient in a Phase 2b clinical study evaluating HTD1801 for the treatment of nonalcoholic steatohepatitis (NASH).

This double-blind, randomized, placebo-controlled, multicentre Phase 2b study will evaluate the effect of HTD1801, 1250 mg twice daily (BID), compared to placebo BID on histologic improvement in adult subjects with NASH and liver fibrosis who also have type 2 diabetes mellitus (“T2DM”) or pre-diabetes. The study will enroll approximately 210 subjects with biopsy-confirmed NASH and evidence of stage 2 or stage 3 liver fibrosis. Subjects will receive HTD1801 for up to 60 weeks.

“Nonalcoholic fatty liver disease (“NAFLD”) is the most prevalent chronic liver disease worldwide with a global prevalence of 25.2% to 29.8%. Of those with NAFLD, about 20% have NASH. Patients with NASH and T2DM or prediabetes are at increased risk of progressive liver disease and cardiometabolic complications,” said Dr. Liping Liu, founder and Chief Executive Officer of HighTide. “This first patient dosing marks a key milestone for the development of HTD1801 for the treatment of patients with NASH, building on data from our Phase 2a study which showed HTD1801 was associated with meaningful improvements in liver fat, markers of liver Injury and fibrosis as well as cardiometabolic factors (HbA1c, lipids, and weight) after 18 weeks.”

About NASH
NASH, a severe form of nonalcoholic fatty liver disease (NAFLD), is a chronic, complex liver disease characterized by hepatitis – inflammation of the liver – and liver cell damage, which can lead to fibrosis of the liver. NASH can also lead to cirrhosis and liver cancer. NASH patients with T2DM or impaired glucose tolerance are more likely to progress to more severe disease and to develop complications that lead to increased mortality. Prevalence of NASH is on the rise and may soon surpass hepatitis C as a cause for liver transplant in the U.S. and Europe. Currently, there are no approved therapies for NASH.

About HighTide Therapeutics
HighTide is a globally integrated clinical-stage biopharmaceutical company focusing on the discovery and development of novel multifunctional therapies for metabolic and digestive diseases with significant unmet medical needs. The company’s lead drug candidate, HTD1801, is a first-in-class new molecular entity, currently in clinical development for the treatment of type 2 diabetes (T2DM), nonalcoholic steatohepatitis (NASH), severe hypertriglyceridemia (SHTG), and primary sclerosing cholangitis (PSC). HTD1801 has received Fast Track designation from the U.S. FDA for both NASH and PSC, as well as Orphan Drug designation for PSC. In China, HTD1801 has been included in the National Major New Drug Innovation Program. For more information, please visit www.hightidetx.com.

Contacts
Nadia Gao
ir@hightidetx.com

• Global biopharmaceutical company focusing on metabolic and digestive diseases
• Proceeds to fund clinical and business development

HighTide Therapeutics Inc. (HighTide), a globally integrated clinical-stage biopharmaceutical company developing novel multifunctional therapies for metabolic and digestive diseases, today announced the closing of a $107 million Series C/C+ financing led by the TCM Healthcare Fund of Guangdong, managed by China Development Bank Capital. Other investors included Yuexiu Fund and Yuthai Fund.

Proceeds of the financing will be used to advance multiple global development programs, including mid-to-late-stage clinical trials, and the commercialization and business development of the company’s robust pipeline. HighTide’s lead candidate HTD1801, is a novel multifunctional molecule, being developed for the treatment of patients suffering from complex metabolic and digestive diseases.

HighTide has successfully completed multiple clinical trials of HTD1801 and continues to advance its global development programs as follows:

• A Phase 2 clinical study in type 2 diabetes (T2DM) is near completion;
• A Phase 2b clinical study in nonalcoholic steatohepatitis (NASH) has been initiated; and
• A successful End-of-Phase 2 (EOP2) meeting was held with the U.S. Food and Drug Administration (FDA) based on the positive findings from the Phase 2 clinical study in primary sclerosing cholangitis (PSC).

“After completing a successful $60 million Series B+ round at the end of 2020, we are thrilled to have well-recognized investors participate in our C/C+ round. We are grateful that our investors have such strong confidence in HighTide’s team, the commercial value of our pipeline, and future development prospects,” said Liping Liu, Ph.D., founder and Chief Executive Officer of HighTide. “The Series C/C+ financing is a significant milestone for HighTide. It will enable us to move aggressively to accelerate the clinical and commercial development of our innovative pipeline and external business collaborations.”

About HighTide Therapeutics
HighTide is a globally integrated clinical-stage biopharmaceutical company focusing on the discovery and development of novel multifunctional therapies for metabolic and digestive diseases with significant unmet medical needs. The company’s lead drug candidate, HTD1801, is a first-in-class new molecular entity, currently in clinical development for the treatment of type 2 diabetes (T2DM), nonalcoholic steatohepatitis (NASH), severe hypertriglyceridemia (SHTG), and primary sclerosing cholangitis (PSC). The U.S. Food and Drug Administration (FDA) granted Fast Track designation to HTD1801 for both NASH and PSC, as well as Orphan Drug designation for PSC. In China, HTD1801 has been included in the National Major New Drug Innovation Program. For more information, please visit www.hightidetx.com.

Contacts:
Investors
Nadia Gao
ir@hightidetx.com
+86-134-8219-0265

Media
Karl Schmieder
karl@messaginglab.com
+1-646-515-3392