nepicastat (APL-1401) / Asieris, Acorda - LARVOL DELTA

First-in-Class DBH Inhibitor Shows Promise for Moderate-to-Severe Active Ulcerative Colitis (DocWire) - "Primary end points included adverse events (AEs), serious AEs, and AEs of special interest. Secondary end points included clinical response and histologic improvement. Clinical response was defined as at least 30% and at least 2-point reduction in the modified Mayo score and at least 1-point decrease in rectal bleeding subscore or a subscore of 0/1. Central laboratory dual readers adjudicated clinical response and histologic improvement....Of the 12 evaluable patients, 5 (41.7%) achieved histologic improvement. There were numerically higher clinical responses (33.3% vs 12.5%) and histologic improvement (66.7% vs 33.3%) in the 120 mg cohort compared with the 160 mg cohort. There were no instances of histologic improvement of clinical response among the patients in the placebo group."

P1 data • Ulcerative Colitis

SAFETY AND EARLY EFFICACY SIGNALS OF THE FIRST-IN-CLASS DOPAMINE Β-HYDROXYLASE INHIBITOR APL-1401 IN MODERATE-TO-SEVERE ACTIVE ULCERATIVE COLITIS: PRIMARY RESULTS FROM A 4-WEEK RANDOMIZED PHASE 1B TRIAL (CCCongress 2026) - P1b | "The 120 mg dose of APL-1401 demonstrated a favorable safety profile and early signals of efficacy in patients with moderate-to-severe active UC during this 4-week MRCT. These findings support further evaluation of the 120 mg dose of APL-1401 in an extended 12-week study."

Clinical • P1 data • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Herpes Zoster • Hypertension • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • Varicella Zoster

First-in-human Phase 1b Study of the Dopamine β-Hydroxylase Inhibitor APL-1401 in Patients with Moderate-to-Severe ULCERATIVE COLITIS: Pharmacokinetics and Preliminary Results (ECCO-IBD 2026) - P1b | "Endoscopic improvement signals were observed in the 120 mg cohort, with 33.3% achieving a 1-point reduction in the Mayo Endoscopic Subscore (MES) and all patients (100%) exhibiting a 1-point reduction in rectal bleeding subscores. Conclusion APL-1401 120 mg QD was well tolerated and demonstrated promising efficacy signals in patients with moderate-to-severe UC over 4 weeks, supporting further evaluation in a 12-week study."

Clinical • First-in-human • P1 data • PK/PD data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Nepicastat: a versatile therapeutic agent - pharmacological activities and clinical prospects. (PubMed, Eur J Pharmacol) - "Nepicastat (NEP) is a popular, highly selective inhibitor of dopamine β-hydroxylase (DBH) being more selective than disulfiram, which is clinically employed in the treatment of alcohol use disorders. Consequently, NEP has attracted growing scientific interest as a candidate for drug repurposing. In this article, we provide a comprehensive overview of the current state of knowledge surrounding NEP, highlighting its diverse pharmacological actions and emerging potential across a range of therapeutic areas."

Journal • Review • Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Oncology • Psychiatry • Substance Abuse

Asieris’ New Drug APL-1401 Demonstrates Positive Preliminary Results in Phase Ib Clinical Trial for Moderately-to-Severely Active UC (Asieris Pharma Press Release) - P1b | N=36 | NCT05743010 | Sponsor: Jiangsu Yahong Meditech Co., Ltd aka Asieris | "Asieris Pharmaceuticals...announced that its oral drug APL-1401 has demonstrated positive preliminary results in a Phase Ib clinical trial for the treatment of moderately-to-severely active ulcerative colitis (UC)...The dose escalation phase has been completed, demonstrating a favorable safety profile. Positive efficacy signals were observed within the short treatment period of only four weeks. Based on these positive results, the company plans to further evaluate the efficacy of this potential first-in-class therapy over a 12-week treatment period in a larger cohort of patients with moderately-to-severely active UC. This will provide more comprehensive supportive data for subsequent clinical studies, with the aim of offering patients a new treatment choice in the future."

P1 data • Ulcerative Colitis

Exploring Nepicastat Activity: Beyond DβH. (PubMed, Int J Mol Sci) - "Its effectiveness was also reported in opioid treatment, as disulfiram attenuated morphine-induced tolerance and dependence. These results clearly indicate nepicastat as a potent molecule that exhibits various biological effects. This, in turn, suggests its possible application in pathological conditions that still require effective treatment."

Journal • Addiction (Opioid and Alcohol) • Pain

Role of β-adrenergic signaling and the NLRP3 inflammasome in chronic intermittent hypoxia-induced murine lung cancer progression. (PubMed, Respir Res) - "Our study underscores the significant contribution of β-adrenergic signaling and the NLRP3 inflammasome to CIH-induced lung cancer progression. These pathways represent potential therapeutic targets for mitigating the impact of OSA on lung cancer."

IO biomarker • Journal • Preclinical • Lung Cancer • Obstructive Sleep Apnea • Oncology • Respiratory Diseases • Sleep Disorder • Solid Tumor • CCND1 • CD31 • IFNG • IL10 • IL1B • IL6 • KDR • NLRP3 • PD-L1 • PECAM1 • TNFA

Effects of acute inhibition of dopamine β-hydroxylase on neural responses to pups in adult virgin male California mice (Peromyscus californicus). (PubMed, Behav Brain Res) - "In contrast, nepicastat did not alter c-Fos expression in any of the above brain regions following exposure to a novel object. Overall, these results suggest that the noradrenergic system might influence MeA and MPOA function to promote behavioral interactions with pups in virgin males."

Journal • Preclinical • Mood Disorders • Psychiatry • FOS

Dopamine β-hydroxylase shapes intestinal inflammation through modulating T cell activation. (PubMed, Cell Immunol) - "Modulation of neurotransmitter levels via inhibition of DBH exerted protective effects on progression of murine colitis by modulating the neuro-immune axis. These findings suggested a promising new therapeutic strategy for attenuating intestinal inflammation."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • IFNG • IL6 • TNFA

Asieris' New Drug APL-1401 Completes First Administration in Patient with Moderately to Severely Active UC (PRNewswire) - "Asieris Pharmaceuticals...announced that its oral drug APL-1401 for the treatment of moderately to severely active ulcerative colitis (UC) completed its first administration....The study is a randomized, double-blind Phase Ⅰb study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of APL-1401 in patients with moderate to severely active UC."

Trial status • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Phase 1b Study to Evaluate APL-1401 in Patients With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P1b | N=36 | Recruiting | Sponsor: Jiangsu Yahong Meditech Co., Ltd aka Asieris | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2024 ➔ Apr 2025 | Trial primary completion date: Feb 2024 ➔ Mar 2025

Enrollment open • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Asieris Obtained IND Approval from NMPA for APL-1401, a Drug for the Treatment of Moderately-to-Severely Active Ulcerative Colitis (PRNewswire) - "Asieris Pharmaceuticals...announced that the National Medical Products Administration (NMPA) has approved the Investigational Drug (IND) application for its oral drug APL-1401 for the treatment of moderately-to-severely active ulcerative colitis (UC).The IND application had previously been approved by the U.S. Food and Drug Administration (FDA). The study is a randomized, double-blind Phase Ib study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of APL-1401 in patients with moderate to severely active UC."

New P1 trial • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

UV irradiation modulates appetite and body weight through upregulating norepinephrine in mice (ISID 2023) - "Notably, liquid chromatography/mass spectrometer analyses in the skin revealed that norepinephrine was among the most significantly increased neurotransmitters in UV-irradiated mice, and downregulation of norepinephrine production by dopamine β-hydroxylase inhibitor nepicastat reversed the effects of UV on food intake and body weight. In conclusion, chronic UV irradiation induces NE release resulting in stimulating food intake due to the downregulation of the anorexigenic hormone leptin, but preventing weight gain through the elevation of energy expenditure."

Preclinical • Genetic Disorders • Obesity • LEP

A Phase 1b Study to Evaluate APL-1401 in Patients With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P1b | N=36 | Not yet recruiting | Sponsor: Jiangsu Yahong Meditech Co., Ltd aka Asieris

New P1 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Asieris Obtained IND Approval from US FDA for APL-1401, a New Drug for the Treatment of Moderately-to-Severely Active Ulcerative Colitis (PRNewswire) - "Asieris Pharmaceuticals...today that the U.S. Food and Drug Administration (FDA) has approved the Investigational New Drug (IND) application for its oral drug APL-1401 for the treatment of moderately-to-severely active ulcerative colitis (UC). The company will begin enrollment soon for this clinical study in the United States, and will submit an CTA application to the National Medical Products Administration (NMPA) of China in the near future. The study is a randomized, double-blind Phase Ib study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of APL-1401 in patients with moderate to severely active UC."

IND • New P1 trial • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis