fipaxalparant (AMG 670) / Amgen - LARVOL DELTA

Fipaxalparant: Data from P2 trial (NCT05032066) for IPF in H2 2024 (Amgen) - Q2 2024 Results

P2 data • Idiopathic Pulmonary Fibrosis

Pharmacokinetics of Fipaxalparant, a Small-Molecule Selective Negative Allosteric Modulator of Lysophosphatidic Acid Receptor 1, and the Effect of Food in Healthy Volunteers. (PubMed, Clin Pharmacol Drug Dev) - "At 450 mg, a high-fat meal increased the maximum observed concentration and area under the curve by approximately 1.9- and 2.1-fold, respectively. These results, combined with prior preclinical and phase 2a data, informed dose selection of fipaxalparant 300 mg once and twice daily with a meal for phase 2b studies."

Journal • PK/PD data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Amgen | Trial primary completion date: Jul 2025 ➔ Aug 2024

Trial primary completion date • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

An Open-label Extension Trial of HZNP-HZN-825-301 in Adult Participants With Diffuse Cutaneous Systemic Sclerosis (Diffuse Cutaneous SSc) (clinicaltrials.gov) - P2 | N=246 | Enrolling by invitation | Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland | Trial completion date: Dec 2025 ➔ Jul 2026 | Trial primary completion date: Dec 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

Fipaxalparant: Data from P2 trial (NCT05032066) for IPF in H2 2024 (Amgen) - Q4 2023 Results

P2 data • Idiopathic Pulmonary Fibrosis

A Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=153 | Active, not recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Phase classification: P2b ➔ P2

Phase classification • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

PHARMACOKINECTS STUDY TO EVALUATE DRUG-DRUG INTERACTIONS (DDI) BETWEEN HZN-825 AND PIRFENIDONE/NINTEDANIB (CHEST 2023) - "The study demonstrated no relevant mutual DDI between HZN-825 and pirfenidone/nintedanib at clinical doses. CLINICAL IMPLICATIONS: These data support allowing pirfenidone and nintedanib as concomitant medications with HZN-825 in ongoing/future clinical trials."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

An Open-label Extension Trial of HZNP-HZN-825-301 in Adult Participants With Diffuse Cutaneous Systemic Sclerosis (Diffuse Cutaneous SSc) (clinicaltrials.gov) - P2 | N=246 | Enrolling by invitation | Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland | Recruiting ➔ Enrolling by invitation

Enrollment status • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Trial completion date: Dec 2024 ➔ Jul 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2b | N=153 | Active, not recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Recruiting ➔ Active, not recruiting

Enrollment closed • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

An Open-label Extension Trial of HZNP-HZN-825-301 in Adult Participants With Diffuse Cutaneous Systemic Sclerosis (Diffuse Cutaneous SSc) (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland

New P2 trial • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Trial completion date: Jul 2023 ➔ Dec 2024 | Trial primary completion date: Jul 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2b | N=135 | Recruiting | Sponsor: Horizon Therapeutics Ireland DAC | N=360 ➔ 135 | Trial completion date: Oct 2023 ➔ Jul 2025 | Trial primary completion date: Sep 2023 ➔ Jun 2024

Enrollment change • Trial completion date • Trial primary completion date • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Open-label Study to Evaluate the Efficacy, Safety, Tolerability of HZN-825 in Patients with Diffuse Cutaneous Systemic Sclerosis (clinicaltrialsregister.eu) - P2 | N=240 | Ongoing | Sponsor: Horizon Therapeutics Ireland DAC

New P2 trial • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2; N=300; Recruiting; Sponsor: Horizon Therapeutics Ireland DAC; Not yet recruiting ➔ Recruiting; Phase classification: P2/3 ➔ P2

Enrollment open • Phase classification • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis • CRP

Ministry of Food and Drug Safety, approval of 7 clinical trials including Samil Pharmaceutical’s gastrointestinal motility regulator [Google translation] (Health Korea News) - "The Ministry of Food and Drug Safety approved seven clinical trials...including Samil Pharmaceutical's gastrointestinal motility regulator....Horizon Therapeutics, USA, obtained approval for the phase 2b trial of 'HZN-825', a treatment for systemic sclerosis of the skin, through the clinical trial consignment agency PPD Development PTLD. Efficacy, safety, and tolerability of 'HZN-825' are evaluated in 8 domestic patients with extensive cutaneous systemic sclerosis. The test is conducted at four institutions including Chonnam National University Hospital."

New P2b trial • Immunology • Systemic Sclerosis

Horizon Therapeutics plc Reports Third-Quarter 2022 Financial Results; Increases Full-Year 2022 Net Sales and Adjusted EBITDA Guidance; Increases TEPEZZA and KRYSTEXXA Peak Annual Net Sales Expectations (BioSpace) - "TEPEZZA® (teprotumumab-trbw) Net Sales of $490.9 Million...Increasing TEPEZZA Ex-U.S. Peak Annual Net Sales Expectations to Greater than $1 Billion, Bringing Global Peak Annual Net Sales Expectations to Greater than $4 Billion...Diffuse Cutaneous Systemic Sclerosis Trial: Pivotal Phase 2b trial underway to evaluate HZN-825 in diffuse cutaneous systemic sclerosis."

Commercial • Trial status • Immunology • Ophthalmology • Systemic Sclerosis • Thyroid Eye Disease

HARBOR study design: efficacy, safety and tolerability of HZN-825, an LPAR1 antagonist, in subjects with idiopathic pulmonary fibrosis (ICLAF 2022) - P2b | "This study may be of interest to clinicians and patients seeking trial options in IPF."

Clinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

BEACON study design: efficacy, safety, tolerability and pharmacokinetics of HZN-825, an LPAR1 antagonist, in diffuse cutaneous systemic sclerosis (ICLAF 2022) - P2 | "The data provided by this trial may provide utility for clinicians seeking to treat their patients with intractable dcSSc."

Clinical • PK/PD data • Fibrosis • Immunology • Inflammation • Rheumatology • Scleroderma • Systemic Sclerosis

Horizon Therapeutics plc Reports Third-Quarter 2022 Financial Results; Increases Full-Year 2022 Net Sales and Adjusted EBITDA Guidance; Increases TEPEZZA and KRYSTEXXA Peak Annual Net Sales Expectations (Businesswire) - "Rheumatoid Arthritis Trial: Phase 2 randomized placebo-controlled trial to evaluate dazodalibep in patients with RA. Topline results were announced in May 2022....Data from the trial will be presented at an upcoming medical meeting....Idiopathic Pulmonary Fibrosis Trial: Pivotal Phase 2b trial underway to evaluate HZN-825 in idiopathic pulmonary fibrosis, the most common form of interstitial lung disease."

New trial • P2 data • Idiopathic Pulmonary Fibrosis • Immunology • Rheumatoid Arthritis

A Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2b; N=360; Recruiting; Sponsor: Horizon Therapeutics Ireland DAC

Clinical • New P2b trial • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Chemical route development and optimization of a 5-hydroxy-2,3-dihydro-1H-indene-2-carboxylic acid compound | Poster Board #3316 (ACS-Fall 2022) - "HZN-825 is a selective, orally active, small molecule lysophosphatidic acid 1 (LPA1/Edg-2) receptor inhibitor that has shown favorable effects in animal models of skin fibrosis and is currently in development for the treatment of diffuse cutaneous systemic sclerosis (dcSSc) and interstitial lung disease (ILD) indications.Various PK studies and in vitro ADME experiments have identified one main metabolite of HZN-825. In order to profile this metabolite, it was necessary to develop an efficient chemical process to allow for this molecule to be synthesized on scale. Synthetic challenges and solutions found for the construction of the highly unusual 5-hydroxy-2,3-dihydro-1H-indene-2-carboxylic acid are presented in this poster."

Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

Future Treatment Options in Systemic Sclerosis-Potential Targets and Ongoing Clinical Trials. (PubMed, J Clin Med) - "Increasing knowledge of the processes and mediators involved in systemic scleroderma has led to the initiation of drug trials with therapeutic targets of CD28-CD80/86, CD19, CCL24, CD20, CD30, tumor necrosis factor (TNF), transforming growth factor β (TGF-β), B-cell activating factor (BAFF), lysophosphatidic acid receptor 1 (LPA1 receptor), soluble guanylate cyclase (sGC), Janus kinases (JAK), interleukin 6 (IL-6), endothelin receptor, and autotaxin. Data from clinical trials on these drugs indicate a significant potential for several new therapeutic options for systemic sclerosis in the upcoming future."

Journal • Review • Fibrosis • Immune Modulation • Immunology • Inflammation • Oncology • Rheumatology • Scleroderma • Systemic Sclerosis • CD19 • CD20 • IL6 • TGFB1 • TNFA • TNFRSF8

Horizon Therapeutics plc Announces First Patient Enrolled in Phase 2b Pivotal Trial Evaluating HZN-825 for the Treatment of Idiopathic Pulmonary Fibrosis (IPF) (Businesswire) - "Horizon Therapeutics...announced the first patient has enrolled in a Phase 2b pivotal trial to evaluate its development-stage medicine HZN-825, a lysophosphatidic acid receptor 1 (LPAR1) antagonist to treat people with IPF, the most common interstitial lung disease....The primary endpoint is change in forced vital capacity (FVC) after 52 weeks...Secondary endpoints include the 6-Minute Walk Test (6MWT), the King’s Brief Interstitial Lung Disease (K-BILD) Questionnaire, rate of hospitalization due to respiratory distress, and a composite endpoint of progression-free survival. Enrollment is expected to take approximately two years. 'The enrollment of the first patient in this pivotal study marks an important milestone for development of this potential therapy for these patients and our commitment to fibrotic conditions.'"

Enrollment status • Idiopathic Pulmonary Fibrosis • Immunology

Daewoong Pharmaceutical Starts Development of Diabetes New Drug Complex … Approval from Ministry of Food and Drug Safety [Google translation] (Health Korea News) - "...PPD Development Management PTD LTD has been approved for Phase 2b of Horizon Pharma's 'HZN-825'. To evaluate the efficacy, safety and tolerability of 'HZN-825' in 38 patients with idiopathic pulmonary fibrosis. Implementing institutions are Seoul National University Bundang Hospital, Samsung Seoul Hospital, Asan Medical Center, Seoul National University Hospital."

New P2b trial • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Respiratory Diseases