seralutinib (GB002) / Gossamer Bio, Pulmokine - LARVOL DELTA

YKSW-GB002-R01: Safety, Tolerability, Pharmacokinetics and Immunogenicity Study of GB002 Recombinant Peptide Inhalation Solution in Healthy Subjects (clinicaltrials.gov) - P1 | N=100 | Active, not recruiting | Sponsor: Zhejiang Echon Biopharm Limited | Trial completion date: Jul 2024 ➔ Jul 2026 | Trial primary completion date: May 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date

Seralutinib in Pulmonary Arterial Hypertension: Exploring Mechanisms of Reverse Remodeling Versus Vasodilation (ATS 2025) - No abstract available

Cardiovascular • Pulmonary Arterial Hypertension • Respiratory Diseases

Gossamer Bio Announces Fourth Quarter and Full-Year 2024 Financial Results and Provides Business Update (Businesswire) - "Seralutinib (GB002):...(i) Enrollment is ongoing in the PROSERA Study, a global registrational Phase 3 clinical trial in patients with WHO Functional Class II and III PAH....Topline results from the PROSERA Study are expected in the fourth quarter of 2025; (ii) We expect to activate clinical sites for a registrational Phase 3 PH-ILD clinical trial in the second half of 2025. The planned Phase 3 study will be a randomized, double-blind, placebo-controlled, global clinical trial in PH-ILD patients; (iii) On January 31st, Japan’s Ministry of Health, Labour and Welfare (MHLW), granted seralutinib Orphan Drug Designation for the treatment of PAH. Previously, the Pharmaceuticals and Medical Devices Agency of Japan (PMDA), allowed inclusion of Japanese clinical trial sites in the ongoing Phase 3 PROSERA Study. Subject to final clinical trial results, PROSERA could form the basis of a marketing application in Japan."

New P3 trial • Orphan drug • P3 data: top line • Trial status • Interstitial Lung Disease • Pulmonary Arterial Hypertension

New therapies in pulmonary arterial hypertension: Recent insights. (PubMed, Int J Cardiol Congenit Heart Dis) - "The first section of this paper explores approaches targeting TGF-β signalling, both acting directly on receptors through drugs like Sotatercept and exogenous BMP9, and indirectly, inhibiting the degradation of key receptors, such as BMPR2. Subsequent sections describe treatments that target epigenetic regulators, e.g. poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors and direct BRD4 antagonists, tyrosine kinase inhibitors (Seralutinib), and therapies aimed at inflammation, such as IL-6 inhibitors, CD-20 inhibitors, and monoclonal antibodies that prevent macrophage migration...This review includes both preclinical and clinical trial data that support efficacy, safety and the future potential of such therapies. Collectively, these therapeutic approaches can be valuable in treating PAH by targeting multiple aspects of its pathogenesis, potentially resulting in improved clinical outcomes for patients affected by this debilitating, life-limiting condition."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • BRD4 • CD20 • TGFB1

Gossamer Bio Presented Clinical and Preclinical Data at the Pulmonary Vascular Research Institute 2025 Annual Congress (Businesswire) - "Gossamer Bio, Inc...presented one oral presentation and three posters related to seralutinib at the Pulmonary Vascular Research Institute (PVRI) 2025 Annual Congress that took place January 29th through February 1st in Rio de Janeiro, Brazil."

P2 data • Preclinical • Pulmonary Arterial Hypertension

Gossamer Bio to Present Clinical and Preclinical Data at the Pulmonary Vascular Research Institute 2025 Annual Congress (Businesswire) - "Gossamer Bio, Inc...announced one oral and three poster presentations related to seralutinib at the Pulmonary Vascular Research Institute (PVRI) 2025 Annual Congress taking place January 29th through February 1st in Rio de Janeiro, Brazil."

Clinical data • Preclinical • Pulmonary Arterial Hypertension

Preclinical models support the synergistic potential of seralutinib & sotatercept in treating PAH (PVRI 2025) - No abstract available

Preclinical

Searching for Old and New Small-Molecule Protein Kinase Inhibitors as Effective Treatments in Pulmonary Hypertension-A Systematic Review. (PubMed, Int J Mol Sci) - "Meta-analysis of preclinical results demonstrated seralutinib, sorafenib, fasudil hydrochloride, and imatinib had the most comprehensive effects on PH with anti-inflammatory, anti-oxidant, and anti-proliferative potential. Fasudil demonstrated more than 70% animal survival with the longest experimental period, while dasatinib, nintedanib, and (R)-crizotinib could deteriorate PAH...They also focus on achieving a satisfactory safety profile using innovative inhalation formulations Many small-molecule protein kinase inhibitors are able to control migration, proliferation and survival in PASMCs in preclinical observations. Standardized animal models can successfully reduce inter-study heterogeneity and thereby facilitate successful identification of candidate drugs for further evaluations."

Journal • Review • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CSF1R • FOLR1 • KIT

Phase 1 Studies to Assess Inhaled Seralutinib as a Perpetrator or a Victim of Drug-Drug Interactions in Healthy Participants. (PubMed, Clin Pharmacol Drug Dev) - "In study 1, 24 participants received a cocktail of probe substrates: caffeine (CYP1A2), montelukast (CYP2C8), flurbiprofen (CYP2C9), midazolam (CYP3A), and pravastatin (OATP1B1/1B3), plus digoxin (P-gp) with or without seralutinib. In study 2, 19 participants received seralutinib with/without itraconazole, a strong CYP3A inhibitor, or fosaprepitant, a weak CYP3A inhibitor...Seralutinib is a moderate CYP3A inhibitor and a weak CYP1A2 inhibitor; it slightly inhibits P-gp. Seralutinib exposure is minimally affected by a weak CYP3A inhibitor but is substantially increased by a strong CYP3A inhibitor."

Journal • P1 data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CYP1A2 • CYP2C9

Trial in progress: PROSERA, a phase 3 study of the efficacy and safety of seralutinib in adults with pulmonary arterial hypertension (PAH) (CVCT USA 2024) - No abstract available

Clinical • P3 data • Cardiovascular • Pulmonary Arterial Hypertension • Respiratory Diseases

SERALUTINIB EXHIBITS ANTIFIBROTIC EFFECTS IN HUMAN MODELS OF PULMONARY FIBROSIS: AN EMERGING OPTION FOR GROUP 1 AND 3 PULMONARY HYPERTENSION? (CHEST 2024) - P2 | " In a human precision-cut lung slice (hPCLS) model of pulmonary fibrosis, healthy donor-derived hPCLS cultures were stimulated with a fibrotic cocktail (PDGF-AB, TGF-β, TNF-α, LPA) and treated for 96 hours with vehicle, seralutinib (1-10 µM) or nintedanib (1 µM), a known anti-fibrotic agent. Seralutinib demonstrated dose-dependent anti-fibrotic effects in two models of human pulmonary fibrosis. These data, along with TORREY circulating fibrotic biomarker data, suggest that seralutinib may have therapeutic effects on the fibrotic pathways underlying both WHO Group 1 and Group 3 PH. CLINICAL IMPLICATIONS: Collectively, the data support further investigation of seralutinib as a potential inhaled treatment option for PH diseases characterized by underlying pulmonary vascular and interstitial fibrosis, such as WHO Group 1 and Group 3 PH."

Cardiovascular • Fibrosis • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • COL1A1 • FN1 • KIT • MMP3 • MMP7 • PDGFRA • TGFB1 • TNFA

Open-label Extension Study of Seralutinib in Adult Subjects With PAH (PROSERA-EXT) (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: GB002, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Sustained effect of seralutinib on circulating biomarkers: Lessons from the TORREY phase 2 open-label extension study (ERS 2024) - P2 | "The observed long-term biomarker changes support a sustained effect of seralutinib on pathways relevant to PAH pathogenesis."

Biomarker • Clinical • P2 data • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CCL3 • COL1A1 • IL10 • ITGB2 • KIT • PDGFRA

Sustained benefit with seralutinib treatment: Lessons from the open-label extension (OLE) of the TORREY study (ERS 2024) - P2 | "Conclusions. In 49% of patients with W72 right heart catheterization data, longer-term seralutinib treatment resulted in sustained hemodynamic and 6MWD improvement."

Clinical • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CSF1R • KIT • PDGFRA

Reverse remodeling and anti-proliferative effects of seralutinib in PAH precision-cut lung slices and pulmonary artery smooth muscle cells (ERS 2024) - P3 | "Seralutinib demonstrated reverse remodeling in PAH PCLS. Inhaled seralutinib is in phase 3 development for PAH (PROSERA; NCT05934526)."

Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ID1 • KIT • PDGFB • PDGFRB

Gossamer Bio Announces Data Presentations at the European Respiratory Society Congress 2024 (Businesswire) - "Gossamer Bio...announced two oral presentations and a poster presentation with data relevant to seralutinib at the European Respiratory Society (ERS) Congress 2024, which takes place from September 7th through 11th....'We are thrilled to present additional findings from our Phase 2 TORREY open-label extension study at the European Respiratory Society Conference in Vienna which highlight the sustained effect of seralutinib beyond 24 weeks of treatment'..."

P2 data • Pulmonary Arterial Hypertension

Cardiac Effort Is Less Variable Than Six-minute Walk Distance, Correlates With Hemodynamics and Is Consistent With REVEAL 2.0 Risk Score in a Sub-study of the TORREY Phase 2 PAH Trial (ATS 2024) - P2 | "Technical issues resulted in substantial data loss, such that 14 patients had baseline and Week 12 measures (7 seralutinib, 7 placebo); 13 had Week 24 data (6 seralutinib, 7 placebo)...0 risk score. CE may have potential utility as a noninvasive measure of risk and physiologic response to therapeutic intervention."

P2 data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

TORREY Phase 2 Study of Seralutinib in Pulmonary Arterial Hypertension (PAH): Circulating Biomarkers of Proliferation, Inflammation, and Fibrosis Improve With Treatment (ATS 2024) - P2 | "Conclusion. The observed protein biomarker changes suggest that seralutinib has a significant impact on inflammatory, proliferative, and fibrotic pathways concordant with clinical improvement in PAH patients."

Biomarker • P2 data • Cardiovascular • Fibrosis • Hypertension • Immunology • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • COL1A1 • ENG • FLT1 • IL10

Interim Results From the Phase 1B and Phase 2 TORREY Open-label Extension Study of Seralutinib in Pulmonary Arterial Hypertension (PAH) (ATS 2024) - P1b, P2, P3 | "Inhaled seralutinib was well tolerated for up to 72 weeks. No new safety signals were identified. Further reductions from Week 24 to Week 72 in PVR demonstrated by seralutinib-to-seralutinib patients suggest persistence of treatment effect."

Clinical • P1 data • P2 data • Cardiovascular • Cough • Hypertension • Infectious Disease • Novel Coronavirus Disease • Pain • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CSF1R

Phase I Clinical Study of GB002 Recombinant Peptide Inhalation Solution (clinicaltrials.gov) - P1 | N=100 | Active, not recruiting | Sponsor: Zhejiang Echon Biopharm Limited

New P1 trial

Seralutinib in adults with pulmonary arterial hypertension (TORREY): a randomised, double-blind, placebo-controlled phase 2 trial. (PubMed, Lancet Respir Med) - P2 | "Treatment with inhaled seralutinib significantly decreased PVR, meeting the primary endpoint of the study among patients receiving background therapy for PAH."

Journal • P2 data • Cardiovascular • Cough • Fibrosis • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CSF1R

Open-label Extension Study of GB002 in Adult Subjects With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. | Trial completion date: Jul 2025 ➔ Dec 2027 | Trial primary completion date: Jul 2025 ➔ Dec 2027

Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Evaluation of Seralutinib Treatment Effect Across Four Risk Tools in the TORREY Study in Pulmonary Arterial Hypertension (PAH) (ISHLT 2024) - P2, P3 | "In addition, analysis using the Non-Invasive French tool showed a trend for risk worsening in the placebo group (OR 0.21, p=0.0672).Conclusion Seralutinib treatment resulted in favorable shifts in risk scores, as represented by odds ratios. This analysis was limited by sample size; further evaluation will be conducted in the phase 3 PROSERA study."

Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

ERS International Congress 2023: highlights from the Pulmonary Vascular Diseases Assembly. (PubMed, ERJ Open Res) - "This includes insights into disease modification in pulmonary arterial hypertension and novel therapies such as sotatercept and seralutinib. A comprehensive overview of the complex relationship between acute pulmonary embolism and chronic thromboembolic pulmonary hypertension (CTEPH) is provided along with our current understanding of the molecular determinants of CTEPH. The importance of multidisciplinary and holistic care cannot be understated, and this article also addresses advances beyond medication, with a special focus on exercise training and rehabilitation."

Journal • Cardiovascular • Hypertension • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

Open-label Extension Study of Seralutinib in Adult Subjects With PAH (PROSERA-EXT) (clinicaltrials.gov) - P3 | N=300 | Not yet recruiting | Sponsor: GB002, Inc.

New P3 trial • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases