HSK31858 / Haisco, Chiesi - LARVOL DELTA

Florensocatib in adults with bronchiectasis: the HOPE-BE trial protocol and baseline demographic characteristics. (PubMed, ERJ Open Res) - "Florensocatib (formerly known as HSK31858) is a novel reversible inhibitor of dipeptidyl peptidase 1...Significant geographical variations were seen regarding comorbidity, blood eosinophil counts and sputum bacteriology. The baseline demographic characteristics of the HOPE-BE trial may provide important clues to future therapeutic efficacy assessment in adults with bronchiectasis."

Journal • Bronchiectasis • Infectious Disease • Pulmonary Disease • Respiratory Diseases

A Study to Assess the Safety of HSK31858 in Participants With Non-Cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P3 | N=669 | Recruiting | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New P3 trial • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Clinical Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of HSK31858 in Healthy Subjects (clinicaltrials.gov) - P1 | N=24 | Enrolling by invitation | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Trial primary completion date: Nov 2025 ➔ Nov 2026

Trial primary completion date

Bronchiectasis Treatment Goals, Unmet Needs, and Emerging Therapies: A Podcast. (PubMed, Pulm Ther) - "In the phase 3, 52-week ASPEN trial, brensocatib significantly reduced exacerbation burden, and the 25-mg dose reduced lung function decline and nominally significantly improved patient-reported symptoms compared with placebo. Additional therapies in development include other DPP1 inhibitors (verducatib and HSK31858) and drugs targeting phosphodiesterase 3/4 inhibition (ensifentrine) and anti-interleukin-33 (itepekimab). Overall, the future is promising for patients with the historically neglected and underdiagnosed disease bronchiectasis, with growing awareness and new therapeutic tools becoming available. Podcast (MP4 81554 KB)."

Journal • Bronchiectasis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pediatrics • Pulmonary Disease • Respiratory Diseases • IL33

Clinical Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of HSK31858 in Healthy Subjects (clinicaltrials.gov) - P1 | N=24 | Enrolling by invitation | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New P1 trial

Clinical Study to Evaluate the Effect of Rifampicin on the Pharmacokinetics of HSK31858 in Healthy Subjects (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New P1 trial

Dipeptidyl peptidase 1 inhibitors for inflammatory respiratory diseases: mechanisms, clinical trials, and therapeutic prospects. (PubMed, Front Pharmacol) - "Leading compounds including brensocatib, BI 1291583, and HSK31858 have demonstrated substantial clinical efficacy. Future research priorities include establishing standardized monitoring protocols for dermatological and periodontal health, developing biomarkers for patient stratification, validating long-term safety profiles, and optimizing combination treatment strategies. With brensocatib potentially becoming the first approved mechanism-specific therapy for bronchiectasis by mid-2025, DPP1 inhibitors represent a paradigm shift in managing neutrophil-mediated respiratory diseases."

Journal • Review • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Dipeptidyl peptidase 1 inhibitors and neutrophilic inflammation in bronchiectasis: a narrative review. (PubMed, J Thorac Dis) - "Of these, brensocatib markedly prolonged the time to the first exacerbation and decreased the exacerbation frequency via decreasing the activity of NSPs...Treatment with BI 1291583 reduced the risk of bronchiectasis exacerbations in the phase II Airleaf® trial. HSK31858 significantly decreased the exacerbation frequency and prolonged the time to the first exacerbation in the latest phase II trial among the Chinese population. DPP-1 inhibitors have exhibited promising effects in improving several major clinical outcomes in bronchiectasis via suppressing the activity of NSPs."

Journal • Review • Bronchiectasis • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • CTSC • ELANE

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study of HSK31858 Tablets in Patients with Airway Mucus Hypersecretion in Chronic Airway Inflammatory Diseases (ChiCTR) - P2 | N=309 | Recruiting | Sponsor: Beijing Chao-Yang Hospital, Capital Medical University; Beijing Chao-Yang Hospital, Capital Medical University

New P2 trial • Inflammation

Safety, tolerability, pharmacokinetics and pharmacodynamics of HSK31858, a novel oral dipeptidyl peptidase-1 inhibitor, in healthy volunteers: An integrated phase 1, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study. (PubMed, Br J Clin Pharmacol) - P1 | "HSK31858 was safe and well tolerated. The pharmacokinetics and pharmacodynamics profile of HSK31858 supports further clinical development for the treatment of neutrophil-mediated inflammatory diseases."

Clinical • Journal • P1 data • PK/PD data • Asthma • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • ELANE

Effects of the DPP-1 inhibitor HSK31858 in adults with bronchiectasis in China (SAVE-BE): a phase 2, multicentre, double-blind, randomised, placebo-controlled trial. (PubMed, Lancet Respir Med) - P2 | "Both HSK31858 doses improved clinical outcomes in adults with bronchiectasis, significantly reducing the exacerbation frequency compared with placebo. The development of new drugs targeted at amelioration of neutrophilic inflammation (eg, via suppression of DPP-1 activity) might lead to new options for hindering the progression of bronchiectasis."

Journal • P2 data • Bronchiectasis • Dental Disorders • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases

Haisco plans to raise no more than 1.365 billion yuan through a private placement to invest in new drug research and development projects and replenish cash flow [Google translation] (STCN) - "On the evening of February 27, Haisco (002653) announced its plan to issue A-shares to specific objects in 2025. The company plans to issue no more than 70 million shares to specific objects, and the total amount of funds raised will not exceed 1.365 billion yuan....According to the plan, the research and development of innovative drugs raised by Haisco this time include HSK31679 (non-alcoholic fatty hepatitis), HSK31858 (respiratory diseases), propofol (general anesthesia), HSK39297 (paroxysmal nocturnal hemoglobinuria, primary IgA nephropathy), HSK21542 (postoperative pain, postoperative nausea and vomiting) and HL231 (respiratory diseases) and other drugs for subsequent domestic and overseas clinical research and market registration."

Financing • Anesthesia • Metabolic Dysfunction-Associated Steatohepatitis • Paroxysmal Nocturnal Hemoglobinuria • Respiratory Diseases

A Study to Evaluate the Efficacy and Safety of HSK31858 Tablets in Patients with Airway Mucus Hypersecretion in Chronic Airway Inflammatory Diseases (clinicaltrials.gov) - P2 | N=309 | Enrolling by invitation | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New P2 trial • Asthma • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate the Efficacy and Safety of HSK31858 Tablets in Patients with Bronchial Asthma (clinicaltrials.gov) - P2 | N=219 | Enrolling by invitation | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Observational Study of Sputum Inflammation Phenotypes and Clinical Outcomes in Non-Cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P=N/A | N=400 | Not yet recruiting | Sponsor: Guangzhou Institute of Respiratory Disease

New trial • Bronchiectasis • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Assess the Efficacy and Safety of HSK31858 in Participants With Non-Cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P3 | N=669 | Recruiting | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New P3 trial • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate the Efficacy and Safety of HSK31858 Tablets in Patients with Bronchial Asthma (clinicaltrials.gov) - P2 | N=219 | Not yet recruiting | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New P2 trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Study of HSK31858 in Participants with Non-Cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P2 | N=226 | Completed | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Recruiting ➔ Completed | Trial completion date: Feb 2024 ➔ Jun 2024

Trial completion • Trial completion date • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

…HSK31858 is planned to undergo phase III clinical trials in 2024 [Google translation] (10jqka.com.cn) - "HSK31858 (DPP-1), which treats non-cystic fibrosis bronchiectasis, will conduct domestic Phase III clinical trials in 2024."

New P3 trial • Non‐Cystic Fibrosis Bronchiectasis

Late Breaking Abstract - Phase 2 trial of HSK31858, a novel DPP1 inhibitor, in bronchiectasis (ERS 2024) - "HSK31858 is safe and effective for ameliorating neutrophilic inflammation in bronchiectasis. Figure 1. Time to the first exacerbation (A) and sputum NSPs activity (B)"

Late-breaking abstract • P2 data • Bronchiectasis • Inflammation • Pulmonary Disease • Respiratory Diseases

Mass Balance Study of [14C]HSK31858 in Healthy Adult Male Chinese Subjects. (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Xizang Haisco Pharmaceutical Co., Ltd

New P1 trial

HiSilicon (002653): Obtained the “Drug Clinical Trial Approval Notice“ for the new indication of the innovative drug HSK31858 tablets [Google translation] (CFi.CN) - "Securities code: 002653 Securities abbreviation: Haisco Announcement number: 2024-031 Haisco Pharmaceutical Group Co., Ltd. Announcement on Obtaining the 'Drug Clinical Trial Approval Notice'....HSK31858 is an oral, potent and highly selective small molecule inhibitor of Dipeptidyl Peptidase 1 (DPP1) independently developed by our company. It is intended to be used clinically to treat bronchial asthma."

New trial • Asthma

Announcement of Hisco Pharmaceutical Group Co., Ltd.
on obtaining the “Acceptance Notice“ for the IND application for new indications of innovative drug HSK31858 tablets [Google translation] (Shanghai Securities News) - "Tibet Hisco Pharmaceutical Co., Ltd., a subsidiary of Hisco Pharmaceutical Group Co., Ltd. (hereinafter referred to as the 'Company'), recently received the 'Notice of Acceptance' issued by the State Food and Drug Administration....HSK31858 obtained clinical approval for the indication of 'bronchiectasis (including non-cystic fibrosis bronchiectasis and cystic fibrosis bronchiectasis) and lower respiratory tract diseases caused by acute lung injury/acute respiratory distress syndrome...'"

New trial • Bronchiectasis • Cystic Fibrosis • Non‐Cystic Fibrosis Bronchiectasis

Chiesi Group signed a License Agreement with Haisco Pharmaceutical to develop, manufacture, and commercialise a novel, reversible dipeptidyl peptidase 1 inhibitor for bronchiectasis (PRNewswire) - "Chiesi Farmaceutici S.p.A...and Haisco Pharmaceutical Group Co.Ltd (Haisco Pharmaceutical) today announced the execution of a Licensing Agreement to develop, manufacture, and commercialise outside China and adjacent territories (Hong Kong SAR, Macau SAR and Taiwan District) HSK31858, a novel, reversible dipeptidyl peptidase 1 (DPP1) inhibitor for respiratory diseases....Under the terms of the agreement, Chiesi will make an upfront payment and additional contingent milestone payments to Haisco, including royalties on product sales."

Licensing / partnership • Bronchiectasis

Safety, tolerability, pharmacokinetics(PK) and pharmacodynamics(PD) of HSK31858,a novel DPP-1 inhibitor in healthy volunteers:a phase I clinical trial (ERS 2023) - "HSK31858 exhibited a favorable safety and tolerability profile, and dose-dependently inhibited whole blood NE activity. Figure1. PK profiles of single dose of HSK31858 and mean change in whole blood NE activity; Public health; General respiratory patient care; Pulmonary rehabilitation; Respiratory intensive care; Pulmonary function testing; Epidemiology"

Clinical • P1 data • PK/PD data • Bronchiectasis • Critical care • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases