PIPE-791 / Contineum Therap - LARVOL DELTA

Key Clinical Development Milestones (Businesswire) - "The Company initiated patient dosing in PROPEL-IPF, a global Phase 2 clinical trial evaluating PIPE-791 for the treatment of patients with IPF, in the first quarter of 2026....Johnson & Johnson completed enrollment of 107 adult participants for its Phase 2 MOONLIGHT-1 trial of JNJ-5120/PIPE-307 in June 2026."

Trial status • Idiopathic Pulmonary Fibrosis • Major Depressive Disorder

Contineum Therapeutics Publishes Discovery of Potential Best-in-Class LPAR1 Antagonist PIPE-791 in Journal of Medicinal Chemistry (Businesswire) - "Extensive structural-activity relationship studies led to the identification of a unique scaffold that was responsible for slow but tight binding to LPAR1. Further optimizations that focused on improving brain-penetration and ADME (absorption, distribution, metabolism, excretion) properties afforded PIPE-791....The potential of PIPE-791 to treat both CNS (central nervous system) and peripherally restricted disorders associated with aberrant LPA-LPAR1 signaling was also demonstrated in multiple preclinical disease models."

Preclinical • Idiopathic Pulmonary Fibrosis

Discovery of PIPE-791, A Potent and Brain-Penetrant Lysophosphatidic Acid Receptor 1 Antagonist with Slow Tight Binding Characteristics for the Treatment of Neuroinflammatory Disorders. (PubMed, J Med Chem) - "PIPE-791 possessed excellent ADME properties and was well-tolerated in 28 day GLP (Good Laboratory Practice) toxicity studies in rats and minipigs at doses up to 1000 mg/kg/day. Based on these results and a comprehensive first-in-human enabling preclinical data package, PIPE-791 was advanced into clinical development, including an ongoing trial in subjects with chronic osteoarthritis pain or chronic lower back pain (NCT6810245)."

First-in-human • Journal • Back Pain • Immunology • Inflammation • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

CTX-791-103: Study of PIPE-791 for Subjects With Chronic Osteoarthritis Pain or Chronic Low Back Pain (clinicaltrials.gov) - P1 | N=43 | Completed | Sponsor: Contineum Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Back Pain • Immunology • Lumbar Back Pain • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

PIPE-791 and BMS-986278: Two Lysophosphatidic Acid Receptor 1 (lpa1) Antagonists With Distinct Lung Occupancy Profiles and Vascular Effects (ATS 2026) - No abstract available

Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

LPA1 Antagonism by PIPE-791 Reduces Alveolar Epithelial Cell Apoptosis In Vitro (ATS 2026) - No abstract available

Preclinical • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

LPA1 Expression in CNS Fibroblasts During Multiple Sclerosis (ACTRIMS Forum 2026) - "We had previously shown that PIPE-791 inhibits hMF activation and that ALRs are high in LPA1. FISH confirmed high LPA1 and revealed LPA1/COL1A1+ co-expressing cells at ALRs, implying LPA1-sensitive fibrosis. Next, with TSPO, a known marker of active microglia, we confirm TSPO+ cells at ALRs and show a subset of cells that co-express αSMA, an active fibroblast marker."

CNS Disorders • Fibrosis • Immunology • Inflammation • Multiple Sclerosis • COL1A1 • VIM

Pharmacological Blockade of LPAR1 Does Not Provide Neuroprotection in a Rat Model of Ocular Hypertensive Glaucoma. (PubMed, Transl Vis Sci Technol) - "Here we test the efficacy of PIPE-791, an LPAR1-selective antagonist, in conferring neuroprotection and modulating neuroinflammation in glaucoma...Our data suggests that targeting LPAR1 through pharmacological means does not provide neuroprotection or modulate neuroinflammation favorably in glaucoma. Our study provides evidence that pharmacological targeting of LPAR1 as a potential therapeutic avenue in glaucoma may not be beneficial."

Journal • Preclinical • Cardiovascular • Glaucoma • Inflammation • Ocular Inflammation • Ophthalmology

Study to Evaluate the Efficacy, Safety, and Tolerability of PIPE 791 in Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=324 | Recruiting | Sponsor: Contineum Therapeutics | Not yet recruiting ➔ Recruiting

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

Study to Evaluate the Efficacy, Safety, and Tolerability of PIPE 791 in Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=324 | Not yet recruiting | Sponsor: Contineum Therapeutics

New P2 trial • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Lpa-induced activation of satellite glia cells and its modulation by pipe-791, a novel lpa1 antagonist, in an in vitro pain model (Neuroscience 2025) - "Notably, PIPE-791 significantly reduced the expression of GFAP and FABP7, reinforcing the role of LPA signaling in neuropathic pain and demonstrating that LPA₁ antagonism can effectively attenuate glial activation. Collectively, these findings suggest that PIPE-791 may alleviate pain in vivo by modulating LPA-induced activation of satellite glial cells (SGCs)."

Preclinical • CNS Disorders • Neuralgia • Pain • FABP7 • FAP • GFAP

Cns-penetrant lpa₁ antagonist pipe-791 provides superior analgesia compared to peripherally restricted ctx-343 in a rat model of lpa-induced osteoarthritis (Neuroscience 2025) - "Of note, neuropathic pain can be ameliorated by CNS administration of either an anti-IL-6 antibody or an autotaxin inhibitor. As such, PIPE-791's superior analgesic profile highlights the importance of targeting central LPA₁ signaling and supports further development of CNS-penetrant LPA1 antagonists for OA and neuropathic pain."

Preclinical • CNS Disorders • Musculoskeletal Pain • Neuralgia • Pain • ENPP2 • GFAP

CTX-791-103: Study of PIPE-791 for Subjects With Chronic Osteoarthritis Pain or Chronic Low Back Pain (clinicaltrials.gov) - P1 | N=43 | Active, not recruiting | Sponsor: Contineum Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Back Pain • Immunology • Lumbar Back Pain • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Key Clinical Development Milestones (Businesswire) - "The Company expects to report topline data from its ongoing PIPE-307 Phase 2 VISTA RRMS trial in the fourth quarter of 2025....Contineum is proceeding with activities supporting the launch of its planned global PIPE-791 Phase 2 clinical trial in IPF. This trial is expected to be initiated in the fourth quarter of 2025."

New P2 trial • P2 data • Idiopathic Pulmonary Fibrosis • Immunology • Multiple Sclerosis

Contineum Therapeutics Reports Positive Topline Data From Phase 1b Positron Emission Tomography (PET) Trial of PIPE-791 (Businesswire) - "A PK relationship between PIPE-791 exposure and LPA1 brain RO was confirmed in healthy volunteers and PrMS patients; Plasma EC50 values 37 ng/mL at 24 hours and 12 ng/mL at 168 hours post-dose demonstrate sustained target engagement in healthy volunteers; The Company believes its planned doses for its future Phase 2 proof-of-concept clinical trials will exceed 90% target coverage at trough with once daily dosing."

New P2 trial • P1 data • PK/PD data • Multiple Sclerosis

The LPAR1 antagonist, PIPE-791 produces antifibrotic effects in models of lung fibrosis. (PubMed, Respir Res) - "We show that PIPE-791 effectively reduces fibrosis and fibrotic markers in vitro and in vivo and that it has slow association and dissociation kinetics. Taken together, our data support clinical testing of PIPE-791 in the context of fibrotic conditions such as IPF."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Reduced activation of pain-related brain regions with lysophosphatidic acid receptor subtype-1 antagonist PIPE-791 in a nonhuman primate model of chronic peripheral neuropathy. (PubMed, Neuropharmacology) - "Evoked brain activation could be related to painful peripheral neuropathy and reduced brain activation could be a direct indicator of reduced pain perception following treatment. The current findings suggest decreasing neuroinflammation by blocking LPA1Rs could be a novel approach to the management chronic painful peripheral neuropathy."

Journal • Preclinical • Inflammation • Neuralgia • Pain • Peripheral Neuropathic Pain

CTX-791-102: PET Study of PIPE-791 in Healthy Volunteers and Volunteers With PrMS and IPF (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Contineum Therapeutics | Recruiting ➔ Completed | N=28 ➔ 16

Enrollment change • Trial completion • CNS Disorders • Idiopathic Pulmonary Fibrosis • Immunology • Multiple Sclerosis • Pulmonary Disease • Respiratory Diseases

Contineum Therapeutics Reports Second-Quarter 2025 Financial Results; Updates Key Clinical Development Milestones (Businesswire) - "The Company is proceeding with activities related to the submission of regulatory applications with foreign regulatory authorities, and with the U.S. Food & Drug Administration (FDA), in support of its planned global PIPE-791 Phase 2 proof-of-concept clinical trial in IPF. This trial is expected to be initiated in the fourth quarter of 2025....Research and development expenses were $14.1 million, a 78 percent increase from the second quarter of 2024, largely due to higher clinical development expenses related to the advancement of the Company’s PIPE-791..."

Commercial • New P2 trial • Idiopathic Pulmonary Fibrosis

Contineum Therapeutics Provides Update on Phase 1b Positron Emission Tomography (PET) Trial of PIPE-791 (Businesswire) - "Contineum Therapeutics...announced an update on its Phase 1b positron emission tomography (PET) trial of PIPE-791, a selective antagonist of the lysophosphatidic acid 1 (LPA1) receptor. The Company has completed enrollment of the healthy volunteer and progressive multiple sclerosis (PrMS) cohorts of this trial. The screening and enrollment of idiopathic pulmonary fibrosis (IPF) patients to participate in this trial is ongoing....'We now anticipate reporting topline data from these fully enrolled cohorts in the third quarter of 2025'....The Phase 1b, open label, single-center trial is designed to assess the correlation between pharmacokinetics and LPA1 receptor occupancy using PET imaging in healthy volunteers, as well as IPF and PrMS patients. To date, 12 healthy volunteers and four PrMS patients have participated in this trial."

P1 data • Trial status • Idiopathic Pulmonary Fibrosis • Multiple Sclerosis

Contineum Therapeutics Reports First-Quarter 2025 Financial Results; Affirms Key Clinical Development Milestones (Businesswire) - "Topline data from PIPE-791 Phase 1b positron emission tomography (PET) trial expected in the second quarter of 2025; PIPE-791 chronic toxicity studies completed to support future Phase 2 trials; Topline data from PIPE-307 Phase 2 VISTA trial for the treatment of relapsing-remitting multiple sclerosis (RRMS) anticipated in the second half of 2025...The Company plans to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for CTX-343 in the second half of 2025."

Clinical data • Idiopathic Pulmonary Fibrosis • Lumbar Back Pain • Multiple Sclerosis • Osteoarthritis • Pain

Contineum Therapeutics Reports First-Quarter 2025 Financial Results... (Businesswire) - "Research and development expenses were $13.7 million, a 76 percent increase from the first quarter of 2024, largely due to higher clinical development expenses related to the advancement of the Company’s PIPE-791 and PIPE-307 programs and higher employee-related costs. The Company continues to believe its full-year 2025 research and development expenses will be significantly higher when compared to the full-year 2024 due to a meaningful increase in clinical development activity across its pipeline."

Commercial • Idiopathic Pulmonary Fibrosis • Multiple Sclerosis • Pain

Contineum Therapeutics Reports...Affirms Key Clinical Development Milestones (Businesswire) - "Contineum expects topline data from its PIPE-791 Phase 1b PET trial in the second quarter of 2025...Contineum plans to initiate Phase 2 proof-of-concept clinical trials in IPF and PrMS in the second half of 2025...The Company anticipates topline data from its PIPE-791 Phase 1b chronic pain trial in early 2026...Contineum expects topline data from its PIPE-307 Phase 2 VISTA RRMS trial in the second half of 2025...The Company plans to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for CTX-343 in the second half of 2025."

Clinical data • IND • New P2 trial • Idiopathic Pulmonary Fibrosis • Multiple Sclerosis • Pain

Contineum Therapeutics Initiates Patient Dosing in Phase 1b Chronic Pain Trial of PIPE-791 (Businesswire) - "Contineum Therapeutics...initiated patient dosing in its exploratory PIPE-791 Phase 1b, randomized, double-blind, placebo-controlled, crossover, chronic pain trial....PIPE-791 is being evaluated for the treatment of chronic pain associated with two separate indications, osteoarthritis (OA) and low back pain (LBP). The Company expects to enroll approximately 40 patients at up to five sites in the U.S., and a treatment duration of 28 days. Contineum anticipates topline data from the PIPE-791 Phase 1b chronic pain trial in early 2026."

P1 data • Trial status • Back Pain • Osteoarthritis • Pain

CTX-791-103: Study of PIPE-791 for Subjects with Chronic Osteoarthritis Pain or Chronic Low Back Pain (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Contineum Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Back Pain • Immunology • Lumbar Back Pain • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology