Traficet-EN (vercirnon) / Amgen - LARVOL DELTA

Imaging of CCR9 in the small bowel of patients with Crohn’s disease: effects of the CCR9-depleting monoclonal antibody AZD7798 (ECCO-IBD 2025) - P1 | "Here we use positron emission tomography (PET) with a novel CCR9-specific PET tracer, [ 11 C]vercirnon, to assess the ability of AZD7798 to deplete CCR9+ cells in the intestines of healthy volunteers and patients with SBCD. The study demonstrates the value of molecular imaging for understanding treatment effect in the target tissue in vivo . An ongoing PET imaging study will assess the effects of AZD7798 on CCR9+ cell depletion/repletion in the gut following multiple doses, alongside Phase 2 studies evaluating the clinical efficacy of AZD7798 in moderate-to-severe Crohn’s disease."

Clinical • Crohn's disease • Immunology • Inflammation • Inflammatory Bowel Disease

First-time-in-human visualisation of CCR9 expression in the gut by positron emission tomography (SNMMI 2024) - P1 | "To address this need, we have developed a CCR9-specific PET tracer based on the small molecule CCR9 antagonist vercirnon. We have developed a CCR9-specific PET tracer which potentially enables repeatable quantification of CCR9 expression in the gut. Ongoing studies will use the PET tracer assess the effects of AZD7798 on CCR9+ cell depletion/repletion in the gut, providing critical data to support the clinical development programme."

Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

FIRST-TIME-IN-HUMAN VISUALISATION OF CCR9 EXPRESSION IN THE GUT BY POSITRON EMISSION TOMOGRAPHY (DDW 2024) - P1 | "To address this need we have developed a CCR9-specific PET tracer based on the small molecule CCR9 antagonist vercirnon. Conclusion :We have developed a CCR9-specific PET tracer which potentially enables repeatable quantification of CCR9 expression in the gut. Ongoing studies will assess the effects of AZD7798 on CCR9+ cell depletion/repletion in the gut providing critical data to support the clinical development programme."

Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

First-time-in-human visualisation of CCR9 expression in the gut by positron emission tomography. (ECCO-IBD 2024) - P1 | "To address this need, we have developed a CCR9-specific PET tracer based on the small molecule CCR9 antagonist vercirnon. Conclusion We have developed a CCR9-specific PET tracer which potentially enables repeatable quantification of CCR9 expression in the gut. Ongoing studies will assess the effects of AZD7798 on CCR9+ cell depletion/repletion in the gut, providing critical data to support the clinical development programme."

Crohn's disease • Immunology • Inflammatory Bowel Disease

CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinoma via the PI3K/AKT signaling pathway. (PubMed, PeerJ) - "Vercirnon was used as an inhibitor of CCR9, and LY294002 was used as an inhibitor of the PI3K/AKT pathway in this study. The in vivo data from the xenograft mouse models further proved that CCL25 administration promoted malignant tumor progression by activating the PI3K/AKT pathway. The interaction of CCL25 and CCR9 promotes tumor growth and metastasis in SACC by activating the PI3K/AKT signaling pathway, offering a promising strategy for SACC treatment."

IO biomarker • Journal • Adenoid Cystic Carcinoma • Oncology • Solid Tumor • BCL2 • CCND1 • SNAI2

A Chemical Biology Toolbox Targeting the Intracellular Binding Site of CCR9: Fluorescent Ligands, New Drug Leads and PROTACs. (PubMed, Angew Chem Int Ed Engl) - "Starting from vercirnon, an intracellular C-C chemokine receptor type 9 (CCR9) antagonist and previous phase III clinical candidate for the treatment of Crohn's disease, we developed a chemical biology toolbox targeting the IABS of CCR9...To chemically induce CCR9 degradation, we then developed the first PROTAC targeting the IABS of GPCRs. In a proof-of-principle study, we succeeded in showing that our CCR9-PROTAC is able to reduce CCR9 levels, thereby offering an unprecedented approach to modulate GPCR activity."

Journal • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • Targeted Protein Degradation

The role of the CCL25-CCR9 axis in beta-cell function: potential for therapeutic intervention in type 2 diabetes. (PubMed, Metabolism) - "We have shown that CCL25 acts via the Gαi-coupled receptor CCR9 to impair beta-cell function by inhibiting insulin secretion and promoting cytokine-induced apoptosis. Upregulation of CCR9 in islets in obesity, possibly secondary to accumulation of passenger immune cells, may predispose to metabolic dysfunction and our data suggest that CCL25 downregulation or CCR9 inhibition could be explored to treat T2D."

Journal • Diabetes • Genetic Disorders • Immunology • Inflammation • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • CCL5

A study to investigate the efficacy and safety of GSK1605786A in the treatment of subjects with moderately-to-severely active Crohn's disease (SHIELD-1) (clinicaltrials.gov) - P3, N=600; Sponsor: GlaxoSmithKline; Recruiting -> Active, not recruiting.

Enrollment closed • Inflammatory Bowel Disease

ChemoCentryx's CEO discusses Q4 2013 results - Earnings call transcript (SeekingAlpha) - "Our goal is to seek a partner for vercirnon, possibly along with our second generation CCR9 inhibitor CCX507 in the treatment of inflammatory bowel disease..."; Anticipated completion of CCX507 P1 program in H1 2014.

Anticipated licensing / partnership • Anticipated trial completion date • Immunology • Inflammatory Bowel Disease

GSK: Q2 2013 Results (GSK) - Anticipated data from P3 trial for Crohn's disease in 2013/2014

Anticipated P3 data • Inflammatory Bowel Disease

Vercirnon ‘not safe and effective’ for induction in Crohn’s disease (Gastroendonews) - P3, N=608; NCT01277666; "The primary end point (CDAI score reduction ≥100) was achieved by 27.2% of patients in the vercirnon twice-daily group, 27.6% in the vercirnon once-daily group and 25.1% in the placebo group. Remission occurred in 15.3%, 13.3% and 12.9% of patients, respectively. There was no difference in CRP and fecal calprotectin levels from baseline to week 12."

P3 data • Inflammatory Bowel Disease

ChemoCentryx: Q2 2013 Results (Chemocentryx) - Anticipated top-line data from P3 SHIELD-1 trial for Crohn's disease in early Q4 2013

Anticipated P3 data: top line • Crohn's Disease • Immunology • Inflammatory Bowel Disease

Q3 2012 Results (Chemocentryx) - Anticipated data from four registrational P3 trials, including SHIELD-1, a pivotal induction study for Crohn's disease, in 2013.

Anticipated P3 data • Immunology • Inflammatory Bowel Disease

Vercirnon for the treatment of Crohn's disease (Expert Opin Investig Drugs) - PMID: 23627683; "This review details the current research on CCR9 antagonism and summarizes available clinical trial data for vercirnon , a selective CCR9 antagonist currently under development... CCR9 antagonism may have comparable efficacy to anti-TNF therapies and a potentially superior safety profile...since vercirnon is an oral drug, its associated costs will likely be much lower than expensive infusion-based anti-TNF therapies, providing further economic benefits."

Review • Inflammatory Bowel Disease

Single and repeat dose pharmacokinetic study of GSK1605786 in healthy Chinese subjects (clinicaltrials.gov) - P1, N=22; Sponsor: GlaxoSmithKline; Not yet open; New P1 trial.

New P1 trial • Inflammatory Bowel Disease

SHIELD 4 phase 3 clinical trial with orally administered CCR9 inhibitor vercirnon in Crohn’s disease (ACG 2014) - Presentation time: time: Monday, Oct 20, 10:30 AM – 10:30 AM; Abstratct #P1049; P3, N=253; Sponsor: GlaxoSmithKline; SHIELD-4 (NCT01536418); “The incremental increase in response and remission rates with the higher dose of vercirnon is dissimilar to the data from the SHIELD 1 study, but similar to data from the Phase 2b PROTECT-1 study. These data suggest that, consistent with the mechanism of action, a gradual onset of clinical effect may be observed, particularly with the higher dose of vercirnon.”

P3 data • Inflammatory Bowel Disease

ChemoCentryx: Analyst Day (Chemocentryx) - "Vercirnon, But Not Placebo, Exhibited a CDAI Remission Rate of ~50% During Maintenance Period"; "4% Vercirnon Subjects in Steroid-Free CDAI Remission at Week 52 (P < 0.05)"

P2 data • Crohn's Disease • Immunology • Inflammatory Bowel Disease

A randomized controlled trial of the efficacy and safety of CCX282-B, an orally-administered blocker of chemokine receptor CCR9, for patients with Crohn’s disease (PLoS One) - P2, N=436; Sponsor: ChemoCentryx; NCT00306215; "At week 12, response rates were 47%, 56% (...p = .168), 49% (...p = .792), and 61% (...p = .039), respectively. At the end of the Maintenance period (week 52), 47% of subjects on CCX282-B were in remission, compared to 31% on placebo (...p = .012); 46% showed sustained clinical responses, compared to 42% on placebo (...p = .629)."

P2 data • Inflammatory Bowel Disease

CCR9 inhibitor vercirnon clinical trials in Crohn's disease (UEGW 2014) - Presentation time: Wednesday, October 22, 2014; Time: 09.00-17.00; Abstract #P1466; P2b, N=436; PROTECT-1; P3, N=608; SHIELD 1; "The most significant difference was the higher incidence of prior TNF inhibitor use in SHIELD-1 (69%) compared to PROTECT-1 (26%). Also, PROTECT-1 enrolled patients with more severe disease at baseline (CRP and CDAI higher)....These results suggest activity at the 500 mg QD dose, shown efficacious in PROTECT-1. The higher 500 mg BID dose was associated with a higher incidence of GI AEs...which may increase the CDAI."

Retrospective data • Inflammatory Bowel Disease

ChemoCentryx announces financial results for the quarter ended March 31, 2013 (Chemocentryx) - P3, N=600; Sponsor: GlaxoSmithKline; SHIELD-1 (NCT01277666); "...top-line data readout from the SHIELD-1 Phase III clinical trial in Crohn's disease expected 2H 2013 with partner GlaxoSmithKline..."

Anticipated P3 data • Inflammatory Bowel Disease

GSK announces phase III study of vercirnon in patients with moderate-to-severe Crohn’s disease did not meet its primary endpoint (GSK Press Release) - P3, N=608; Sponsor: GlaxoSmithKline; SHIELD-1 (NCT01277666); "The rates of serious adverse events and withdrawals due to adverse events were similar among the treatment groups, but there was a trend for dose-dependent increases in overall adverse event rates....The full results from the SHIELD-1 study will be submitted to a forthcoming scientific congress and peer-reviewed scientific journal."

Anticipated P3 data • P3 data • Crohn's Disease • Inflammatory Bowel Disease

Interfering with leukocyte trafficking in Crohn's disease. (PubMed, Best Pract Res Clin Gastroenterol) - "Targets for modulators of leukocyte trafficking include (examples in brackets) ICAM-1 (alicaforsen, efalizumab); MAdCAM-1 (PF-00547 659); α4 and related receptors (abrilumab, etrolizumab, natalizumab, vedolizumab); chemokine receptor CCR9 (vercirnon); and sphingosine 1-phosphate receptors (etrasimod, fingolimod, ozanimod). Oral and subcutaneous therapies are in development. The safety, efficacy and practice points of licensed drugs are discussed, in addition to initial results from therapeutic trials."

Journal • Review