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

SERANATA: Efficacy and Safety of Seralutinib in Adult Subjects With Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD) (clinicaltrials.gov) - P3 | N=480 | Recruiting | Sponsor: GB002, Inc. | Not yet recruiting ➔ Recruiting

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

Seralutinib decreases endotrophin (PRO-C6) production, a mediator of fibrosis and inflammation, in an in vitro model of pulmonary fibrosis (ERS 2025) - P2 | "By day 12, seralutinib treatment reduced PRO-C6 levels in a concentration-dependent manner (1.3- to 2.3-fold), with 1000 nM seralutinib reducing PRO-C6 levels to those observed in unstimulated cells. Conclusion Seralutinib decreased PRO-C6 production in an in vitro model of pulmonary fibrosis providing a compelling rationale to further investigate its potential as a surrogate biomarker of pulmonary fibrosis and its role in the pathophysiology of vascular remodeling in PH."

Preclinical • Cardiovascular • Fibrosis • Hepatology • Immunology • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • COL6A3

Seralutinib increases small pulmonary artery vessel volume and reduces vessel wall remodeling: Insights from AI-driven CT imaging analysis (ERS 2025) - "In this exploratory analysis, seralutinib improved metrics of vascular remodeling, correlating with hemodynamic changes. These results support seralutinib's effect on remodeling and highlight the utility of AI-driven CT imaging in treatment evaluation in PAH."

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

Seralutinib shows significant anti-fibrotic effects: Evidence from patient-derived models (ERS 2025) - P2 | " PCLS from two IPF patient donors were cultured and treated for 4 days with vehicle, seralutinib (0.1- 10μM), or nintedanib (1μM). These data support investigation of seralutinib as a potential inhaled treatment option for diseases characterized by underlying pulmonary vascular and interstitial fibrosis, including PH and other ILDs."

Clinical • Cardiovascular • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • KIT • MMP3 • PDGFRA • TIMP1

Seralutinib targets fibrotic pathways in IPF: Evidence from single-cell transcriptomics (ERS 2025) - P2 | "Conclusions. Seralutinib downregulated pathways elevated in IPF disease-relevant cell populations, suggesting a broad, multi-cellular impact on fibrosis, thus supporting the development of seralutinib as a novel inhaled therapy for fibrotic lung diseases."

Cardiovascular • Fibrosis • Idiopathic Pulmonary Fibrosis • Pulmonary Arterial Hypertension • COL1A1 • COL6A3 • ITGB1

Seralutinib demonstrates in vitro reduction of vascular inflammatory drivers underlying pulmonary hypertension (ERS 2025) - P2 | "Conclusions Seralutinib demonstrated broad anti-inflammatory effects across multiple in vitro vascular inflammation models. These findings, combined with clinical biomarker data, highlight seralutinib's potential for reducing the underlying inflammation in PH, and merit further investigation."

Preclinical • Cardiovascular • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CSF2 • CXCL8 • CXCL9 • IFNG • IL17A • IL1B • IL4 • TLR4 • TNFA • VCAM1

SERANATA: Efficacy and Safety of Seralutinib in Adult Subjects With Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD) (clinicaltrials.gov) - P3 | N=480 | Not yet recruiting | Sponsor: GB002, Inc.

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

Seralutinib for the Treatment of Pulmonary Arterial Hypertension in Adults: TORREY Open-Label Extension Study. (PubMed, Adv Ther) - P1b, P2, P3 | "These OLE data are consistent with TORREY results and support long-term safety and efficacy of inhaled seralutinib in patients with PAH. A phase 3 study of seralutinib in PAH is underway (PROSERA, NCT05934526)."

Journal • Cardiovascular • Cough • Hypertension • Infectious Disease • Novel Coronavirus Disease • Pain • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CSF1R • KIT • NPPB

Anticipated 2025 Partner Events of Note - Gossamer Bio (GlobeNewswire) - "Activates first clinical sites for the global, registrational Phase 3 SERANATA Study examining seralutinib in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD) in the fourth quarter."

New P3 trial • Interstitial Lung Disease • Pulmonary Arterial Hypertension

Open-label Extension Study of GB002 in Adult Subjects With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P2 | N=74 | Active, not recruiting | Sponsor: GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. | Recruiting ➔ Active, not recruiting

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

Anti-remodeling therapies in pulmonary arterial hypertension. (PubMed, Trends Pharmacol Sci) - "The approval of sotatercept, the first agent presumed to target vascular remodeling, and the development of seralutinib, an inhaled tyrosine kinase inhibitor (TKI), mark key milestones. In this review, we focus on anti-remodeling therapies that have progressed from preclinical models to clinical trials. These include agents targeting cell cycle regulators, kinase pathways, epigenetic modifiers, bone morphogenetic protein receptor type 2 (BMPR2) signaling, and senescence in pulmonary arterial smooth muscle cells (PASMCs), offering renewed hope for durable PAH treatment."

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

Efficacy and Safety of Seralutinib in Adult Subjects With PAH (PROSERA) (clinicaltrials.gov) - P3 | N=350 | Active, not recruiting | Sponsor: GB002, Inc. | Recruiting ➔ Active, not recruiting

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

Clinical Pharmacokinetics of Inhaled Drugs for Pulmonary Hypertension. (PubMed, Clin Pharmacokinet) - "This review examines the clinical PK characteristics of key inhaled PH drugs (approved and investigational agents), including epoprostenol, iloprost, treprostinil, vardenafil, imatinib, seralutinib, MK-5475, milrinone, and sodium nitrite. Future research would focus on how disease-specific factors affect drug behavior and the prediction of pulmonary drug concentrations. This will support more precise drug delivery and personalized treatment strategies for PH."

Journal • PK/PD data • Review • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Seralutinib in Pulmonary Arterial Hypertension: Exploring Mechanisms of Reverse Remodeling Versus Vasodilation (ATS 2025) - P2, P3 | "In an acute hypoxia-induced vasoconstriction rat model with continuous mean pulmonary artery pressure (mPAP) monitoring, seralutinib (0.2 and 2 mg/kg), treprostinil (6 μg/kg) or vehicle control was administered via intratracheal delivery. Although seralutinib effectively inhibited PDGF-induced calcium flux, it did not exhibit significant vasodilatory effects in the preclinical models of vasoconstriction. These findings suggest that the primary MOA of seralutinib in PAH is reverse remodeling, rather than vasodilation. This supports its role as an anti-proliferative and anti-fibrotic agent differentiated from traditional vasodilator therapies."

Cardiovascular • Pulmonary Arterial Hypertension • Respiratory Diseases • CSF1R

Drugs targeting novel pathways in pulmonary arterial hypertension. (PubMed, Eur Respir J) - "Sotatercept, a fusion protein acting as an activin receptor ligand trap to rebalance growth-promoting and growth-inhibiting signalling has shown promise in clinical trials by reducing pulmonary vascular resistance and improving exercise capacity...Therapies targeting receptor tyrosine kinases (RTKs), such as imatinib, inhibit the platelet-derived growth factor pathway...Novel RTK inhibitors like seralutinib administered by inhalation have shown promising results in a phase 2 clinical trial. Other emerging approaches include anti-inflammatory therapies, hormonal modulation, and metabolism-targeting agents like ranolazine and SGLT2 inhibitors, which could expand the therapeutic landscape for PAH. Overall, the continued development of novel drugs targeting these pathways offers hope for better disease management and improved outcomes for patients with PAH."

Journal • Review • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • TGFB1

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

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