HSK31858 / Haisco, Chiesi - LARVOL DELTA

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

Safety, Tolerability,PK/PD, Food Effect of Single and Multiple Ascending Doses of HSK31858 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=74 | Completed | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New P1 trial • ELANE

Haisco (002653.SZ): Phase II clinical trial of innovative drug HSK31858 tablets completed the first subject enrollment [Google Translation] (Zhitong Finance) - "Haisco...announced that recently, the clinical study of the company's innovative drug HSK31858 tablets 'evaluated the effectiveness and safety of HSK31858 tablets in patients with non-cystic fibrosis bronchiectasis (NCFBE)., placebo-controlled phase II study' completed the enrollment and administration of the first subject....The Phase II clinical research of this project has obtained the ethical approval from the Medical Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University, the team leader, and the Phase II clinical trial has officially started."

Enrollment status • Bronchiectasis • Non‐Cystic Fibrosis Bronchiectasis

A Study of HSK31858 in Participants With Non-Cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Bronchiectasis • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study of HSK31858 in Participants With Non-Cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P2 | N=210 | Not yet recruiting | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New P2 trial • Bronchiectasis • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study of Safety, Tolerability, and Pharmacokinetics of Single Ascending Dosed of HSK31858 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Recruiting ➔ Completed

Trial completion