andecaliximab (GS-5745) / Gilead, ashibio - LARVOL DELTA

Biologic drugs for induction and maintenance of remission in Crohn's disease: a network meta-analysis. (PubMed, Cochrane Database Syst Rev) - "This review has supported evidence generation, but head-to-head comparative trials for key interventional subclasses or specific agents may be needed, as guided by key stakeholders; for example, on the use of biosimilar versions of medications out of patent. The role of concomitant purine analogues is a key confounding factor and future studies may not only want to investigate specifically the role of combinations, but also consider stratifying populations or purposefully excluding participants based on this key class of therapy to avoid such heterogeneity. Given the majority of evidence focusses on the outcomes of clinical remission and relapse, future studies may want to further consider other outcomes of clear interest to clinicians and patients, particularly endoscopic remission. Finally, long-term safety data are limited throughout the networks. Whilst future studies with longer follow-ups could provide increased data, it may be that study designs outside of..."

Clinical • Journal • Retrospective data • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • IL7R

Baseline Characteristics in Part 1 of the ongoing ANDECAL Study, a two-part Phase 2/3 Study of andecaliximab (anti-matrix metalloproteinase-9 mAb) in participants with Fibrodysplasia Ossificans Progressiva (FOP) (ASBMR 2026) - No abstract available

P2/3 data • MMP9

Baseline Characteristics in Part 1 of the ongoing ANDECAL Study, a two-part Phase 2/3 Study of andecaliximab (anti-matrix metalloproteinase-9 mAb) in participants with Fibrodysplasia Ossificans Progressiva (FOP) (ASBMR 2026) - No abstract available

P2/3 data • MMP9

Matrix metalloproteinases in intestinal fibrosis and fibrostenosing Crohn's disease: Current evidence, mechanistic hypotheses, and translational challenges. (PubMed, Inflamm Bowel Dis) - "Despite recent advances, clinical trials of anti-MMP agents such as andecaliximab have yielded limited efficacy, likely attributable to challenges in timing, drug specificity, and outcome assessment. Candidate biomarkers and emerging therapeutic strategies remain investigational, and no MMP-directed approach has yet demonstrated clinical utility for routine fibrosis staging or stricture prevention. Future research directions should prioritize longitudinal human studies, mechanistic elucidation of how MMPs influence fibrosis and/or smooth muscle hyperplasia, improved linkage between tissue biology and imaging, fibrosis-specific endpoints, and rigorous validation before clinical trial translation can be justified."

Journal • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • MMP9

A Study of Andecaliximab in Participants With Fibrodysplasia Ossificans Progressiva (FOP) (clinicaltrials.gov) - P2/3 | N=92 | Active, not recruiting | Sponsor: Ashibio Inc | Recruiting ➔ Active, not recruiting

Enrollment closed

Biological Therapy and Small Molecules for Adults With Crohn's Disease: Systematic Review and Network Meta-Analysis. (PubMed, Pharmacotherapy) - "Alongside infliximab 5 mg/kg (SUCRA 98.6%), 10 mg/kg (92%), and 20 mg/kg intravenous (91.8%), the recently approved drugs guselkumab 1200 mg (83.2%), 600 mg (89.2%), and 200 mg intravenous (90.1%), as well as mirikizumab 600 mg (91.5%) and 1000 mg intravenous (82.4%) presented higher probabilities of disease remission and were associated with increased HRQoL. Drugs such as certolizumab, andecaliximab, fontolizumab, abatacept, and etanercept ranked low for remission (SUCRA < 40%) and presented high probabilities of serious adverse events (over 60%)...Given their safety profile, some anti-TNF drugs should be avoided in practice. Trial Registration: PROSPERO: CRD42024519150."

Journal • Retrospective data • Review • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

āshibio Doses First Patient in Phase 1b Trial of Andecaliximab in Patients with Spinal Cord Injury (SCI) at Risk of Heterotopic Ossification (HO) (Businesswire) - "āshibio...announced that the first participant has been dosed in its Phase 1b clinical trial of andecaliximab in patients with spinal cord injury (SCI). The study, called ANDECA-HO, is evaluating patients who are at risk of developing heterotopic ossification (HO), a condition that causes abnormal bone formation in muscles, tendons, ligaments, and other soft tissues....The Phase 1b trial is an open-label study assessing the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of andecaliximab in up to 10 adults (aged 18-89 years) with a history of traumatic SCI. This study will support a future randomized trial in patients with HO related to SCI and other conditions."

Trial status • CNS Disorders

ANDECA-HO: A Study of Andecaliximab in People With Spinal Cord Injury at Risk for Bone Growth Outside of the Normal Skeleton. (clinicaltrials.gov) - P1/2 | N=10 | Recruiting | Sponsor: Ashibio Inc

New P1/2 trial • CNS Disorders • Orthopedics

Metabolism and Response to Stress Gene Signatures Reveal Ulcerative Colitis Heterogeneity and Identify Patients With Increased Response to Therapy. (PubMed, J Crohns Colitis) - "We identified and evaluated a novel, multi-dimensional signature gene set to characterise previously undefined heterogeneity in patients with UC and identify patients less likely to respond to therapy. This approach offers potential utility to define clinical trial populations, enrich for clinical responders, and identify difficult-to-treat populations for therapeutic development."

Gene Signature • Heterogeneity • Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • IL12A

Inside a Metastatic Fracture: Molecular Bases and New Potential Therapeutic Targets. (PubMed, Cancer Med) - "This paper underscores the importance of advanced molecular biology and transcriptomics in identifying novel therapeutic targets. The integration of these biomarkers with clinical and radiological assessments using artificial intelligence tools could revolutionize the diagnostics and treatment strategies for patients with bone metastases."

Biomarker • Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Musculoskeletal Diseases • Oncology • Orthopedics • Solid Tumor • ISLR • TNFRSF11B

āshibio Doses First Patient in ANDECAL study, a Phase 2/3 Trial of Andecaliximab for Treatment of Fibrodysplasia Ossificans Progressiva (FOP) (Businesswire) - "āshibio...today announced the dosing of the first participant in its ANDECAL study, a Phase 2/3 clinical trial evaluating the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of andecaliximab in patients with fibrodysplasia ossificans progressiva (FOP).'"

Trial status • Genetic Disorders

Systematic Literature Review (SLR) of Randomized Controlled Trials (RCTs) of Treatments for First-Line (1L) Gastric Cancer/Gastroesophageal Junction Adenocarcinoma (GC/GEJ) in Adult Patients (ISPOR-EU 2024) - "Among trials of PD-1/PD-L1 inhibitors (tislelizumab, nivolumab, pembrolizumab, sugemalimab, sintilimab), improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were observed for PD-1/PD-L1 inhibitors plus chemotherapy versus chemotherapy alone at median follow-up times ranging from 11.6 to 54.3 months, with median OS, median PFS, and ORR ranging from 12.5 to 17.45 months, 6.9 to 10.94 months, and 47.3% to 68.6%, respectively...Among other targeted therapies, response and survival benefits compared to chemotherapy were mixed; improvements in response and survival were seen with the CLDN18.2 inhibitor zolbetuximab and the FGFR inhibitor bemarituzumab, while benefits compared to chemotherapy were not seen with cetuximab, ramucirumab, andecaliximab, onartuzumab, rilotumumab, pazopanib, or ipatasertib... PD-1/PD-L1 inhibitors showed improved efficacy compared to chemotherapy for the treatment of 1L GC/GEJ; while other..."

Clinical • IO biomarker • Review • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18 • CTLA4 • HER-2

A Study of Andecaliximab in Participants With Fibrodysplasia Ossificans Progressiva (FOP) (clinicaltrials.gov) - P2/3 | N=92 | Recruiting | Sponsor: Ashibio Inc | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of Andecaliximab in Participants With Fibrodysplasia Ossificans Progressiva (FOP) (clinicaltrials.gov) - P2/3 | N=92 | Not yet recruiting | Sponsor: Ashibio Inc | Initiation date: Aug 2024 ➔ Dec 2024

Trial initiation date

Inhibition of MMP9 as a novel treatment strategy for Fibrodysplasia Ossificans Progressiva (FOP): Safety analysis of the anti-MMP9 antibody Andecaliximab in development for FOP (ASBMR 2024) - No abstract available

Clinical • Late-breaking abstract • Musculoskeletal Diseases • Orthopedics • MMP9

A Study of Andecaliximab in Participants With Fibrodysplasia Ossificans Progressiva (FOP) (clinicaltrials.gov) - P2/3 | N=92 | Not yet recruiting | Sponsor: Ashibio Inc

New P2/3 trial

“METABOLISM AND RESPONSE TO STRESS” (MARS) GENE SIGNATURES REVEAL HETEROGENEITY IN PATIENTS WITH ULCERATIVE COLITIS AND IDENTIFY CHARACTERISTICS OF PATIENTS WITH INCREASED RESPONSE TO THERAPY (DDW 2024) - P2/3, P3 | " Two clinical trial datasets including patients with moderate to severe UC with mucosal biopsy RNA-Sequencing analysis were used: a phase /3 study of andecaliximab (anti-matrix metalloproteinase-9 NCT0 5 0 84) and a phase 3 study of ustekinumab (anti-interleukin-1 / 3 UNIFI NCT0 407 36). We describe the MARS signatures which characterize the heterogeneity of participants with UC clinical trials and identify participants most likely to respond to ustekinumab at baseline. These signatures may be generally useful to predict patient response match therapeutics to patient profiles or identify pathways to target in difficult-to-treat patients."

Clinical • Gene Signature • Heterogeneity • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • MMP9

"Metabolism and Response to Stress" (MARS) gene signatures reveal heterogeneity in patients with Ulcerative Colitis and identify characteristics of patients with increased response to therapy (ECCO-IBD 2024) - P2/3, P3 | "Methods Two clinical trial datasets including patients with moderate to severe UC with mucosal biopsy RNA-Sequencing analysis were used: a phase 2/3 study of andecaliximab (anti-matrix metalloproteinase-9, NCT02520284) and a phase 3 study of ustekinumab (anti-interleukin‑12/23, UNIFI, NCT02407236). Conclusion We describe the MARS signatures which characterise the heterogeneity of participants with UC clinical trials and identify participants most likely to respond to ustekinumab at baseline. These signatures may be generally useful to predict patient response, match therapeutics to patient profiles, or identify pathways to target in difficult-to-treat patients."

Clinical • Gene Signature • Heterogeneity • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • IL12A • MMP9

Text Mining and Drug Discovery Analysis: A Comprehensive Approach to Investigate Diabetes-Induced Osteoporosis. (PubMed, Int J Med Sci) - "After DGI analysis, we identified 7 genes targeted by 11 drugs, which represent candidates for treating DOP. This study unveils ANDECALIXIMAB, SILTUXIMAB, OLOKIZUMAB, SECUKINUMAB, and IXEKIZUMAB as promising potential drugs for DOP treatment, demonstrating the significance of utilizing text mining and pathway analysis to investigate disease mechanisms and explore existing therapeutic options."

Journal • Diabetes • Metabolic Disorders • Orthopedics • Osteoporosis • Rheumatology

Identification of key genes in colorectal cancer diagnosis by co-expression analysis weighted gene co-expression network analysis. (PubMed, Comput Biol Med) - "Taken together, the results of the current study indicated that seven hub genes including COL1A2, COL5A1, COL5A2, SERPINH1, MMP9, SPARC, and COL1A1 which were upregulated in CRC could be used as a diagnostic and progression biomarker of CRC. On the other hand, miR-940 which targets SERPINH1 could be used as a potential biomarker of CRC. More ever, Andecaliximab, Carboxylated glucosamine, Marimastat, Tozuleristide, S-3304, Incyclinide, Curcumin, Prinomastat, Demethylwedelolactone, Bevacizumab, Ocriplasmin , and Collagenase clostridium histolyticum were introduced as therapeutic agents for CRC which their therapeutic potential should be evaluated experimentally."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • COL1A1 • COL1A2 • COL5A1 • COL5A2 • MMP9 • SERPINH1

Promising targeted approaches (DGHO 2019) - "The combination of trifluridine/tipiracil (TAS-102) is a new oral anticancer drug with activity in gastrointestinal cancer...Apatinib is a small-molecule tyrosine kinase inhibitor that selectively inhibits the VEGFR-2 tyrosine kinase...The recent results from a large phase 3 trial with andecaliximab, a monoclonal antibody that inhibits matrix-metalloproteinase-9 (MMP-9), failed to replicate the positive data from a previous study of andecaliximab in combination with chemotherapy in untreated HER2-negative gastric or gastroesophageal junction adenocarcinoma...Randomized clinical studies with zolbetuximab are ongoing. Data on new targeted therapy options (excluding immunotherapy) will be discussed."

Immune monitoring of blood in advanced gastroesophageal adenocarcinoma patients treated with an anti-MMP9 monoclonal antibody in combination with nivolumab. (ASCO-SITC 2020) - P1b; "Background: A phase 1b study was conducted in Japanese patients with >2nd line advanced gastroesophageal adenocarcinoma (GEA) to evaluate the safety, tolerability and explore efficacy and biomarkers, of andecaliximab (ADX), an anti-MMP9 monoclonal antibody, in combination with nivolumab (nivo). The observation that baseline levels of LAG3+CD8+ T cells and DCs were higher in responders is consistent with a prior anti-tumor immune response. Transient decreased peripheral CD8+ T cells might reflect T-cell trafficking into tumor in response to immunotherapy, and increased peripheral CTLA-4+ CD4+ T cells may also relate to tumor-localized response. Although in a very small number of patients, the observations are consistent with early changes in peripheral immune cells that may relate to response to immunotherapy."

Clinical • Combination therapy • IO Biomarker • CD8 • MMP9

Effect of MMP9 inhibition on effector T-cell responses in a PD1-axis refractory model. (ASCO-SITC 2017) - P2; "Inhibition of MMP9 reduces tumor burden and promotes cytotoxic T cell infiltration in a PD1-axis refractory mouse model. The combination of nivolumab and GS-5745, a humanized anti-MMP9 inhibitory antibody, is currently being evaluated in gastric cancer (NCT02864381)."

Preclinical • Biosimilar • Gastric Cancer • Gastrointestinal Cancer • Oncology

A phase II, open-label, randomized study to evaluate the efficacy and safety of andecaliximab combined with nivolumab versus nivolumab alone in subjects with unresectable or recurrent gastric or gastroesophageal junction adenocarcinoma. (ASCO-GI 2019) - P2; "Addition of ADX to NIVO did not improve ORR, PFS, or OS compared with NIVO alone in patients with pre-treated metastatic gastric or GEJ adenocarcinoma. Combination of ADX with NIVO had a favorable safety and tolerability profile."

Clinical • IO Biomarker • P2 data • PD(L)-1 Biomarker

Phase 1b study of andecaliximab (GS-5745, ADX) as monotherapy and in combination with nivolumab (nivo) in Japanese subjects with gastric or GEJ adenocarcinoma. (ASCO-GI 2019) - P1b; "Preliminary safety data demonstrate a manageable safety profile for ADX alone and in combination with nivo. The combination appears to be promising."

Clinical • Combination therapy • Monotherapy • P1 data • PD(L)-1 Biomarker