Cdactin-O (CBM588) / Osel, Miyarisan - LARVOL DELTA

Microbiome and cytokine features are associated with graft-versus-host disease incidence in allogeneic hematopoietic cell transplantation patients (ASH 2025) - P1 | "Methods The cohort consisted of 30 patients; half received Clostridium butyricum MIYAIRI 588 (CBM588) and half received placebo treatment as part of a pilot clinical trial investigating the safety of CBM588 administration in transplant recipients undergoing reduced intensity conditioning regimen (NCT03922035)...Conclusion The link between intestinal microbiota and the incidence of aGVHD could be related with an increase in pro-inflammatory cytokines, such as IL-8 and IL-6, after allo-HCT. Understanding the molecular mechanisms that link specific taxonomic groups, such as Enterococcus and Phocaeicola species, with the triggering of cytokine release could help identify strategies to mitigate the incidence of aGVHD."

Clinical • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Transplantation • CXCL8 • IL10 • IL6 • TNFRSF1A

Poor nutritional intake prior to allogeneic hematopoietic cell transplantation is associated with higher incidence of lower-gastrointestinal graft-versus-host disease (ASH 2025) - P1 | "With acohort of patients from our Center, enrolled on a Clostridium butyricum MIYAIRI 588 (CBM588) pilot trial(NCT03922035), we explored how calorie and protein intake during allo-HCT correlate with microbiomecomposition /and incidence of lower gastrointestinal (GI) graft-versus-host disease (GVHD).Methods...These findings underscorethe need to investigate nutritional intake and clinical outcomes in larger cohorts. It highlights thepotential therapeutic opportunity of early nutritional intervention on microbiome and transplantoutcomes."

Graft versus Host Disease • Immunology • Transplantation

CBM588 in Combination With Nivolumab and Cabozantinib for the Treatment of Advanced or Metastatic Kidney Cancer (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Oct 2025 ➔ Jan 2026 | Trial primary completion date: Oct 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Papillary Renal Cell Carcinoma • Renal Cell Carcinoma • Sarcoma • Solid Tumor • CXCL8

Management of symptomatic uncomplicated diverticular disease (SUDD) of the colon with Clostridium butyricum CBM588 versus rifaximin: a retrospective cross-sectional study. (PubMed, Int J Colorectal Dis) - P=N/A | "In this retrospective comparison, Clostridium butyricum CBM588® demonstrated similar efficacy to rifaximin in preventing diverticulitis, with a potential advantage in subjective symptom improvement. These findings support further prospective studies to explore the role of CBM588® in SUDD management. Trial registration Clinicaltrial.gov reference: NCT06852274."

Clinical • Journal • Observational data • Retrospective data • Gastrointestinal Disorder • Pain

Probiotic Prophylaxis with Clostridium Butyricum for Postoperative Infections Following Lung Resection: A Propensity Score-Weighted Analysis. (PubMed, Ann Thorac Surg) - "Perioperative CBM588 may reduce OSS and all postoperative infections following thoracoscopic anatomical lung resection, suggesting a potential prophylactic benefit."

Journal • Infectious Disease • Lung Cancer • Oncology • Solid Tumor

Prognostic Impact of Clostridium butyricum MIYAIRI (CBM588) in Combination With Pembrolizumab for Advanced Urothelial Carcinoma: A Retrospective Cohort Study. (PubMed, Cancer Rep (Hoboken)) - "These results suggest the effectiveness of the CBM588 combination with ICI treatment in UC."

Journal • Retrospective data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Perioperative administration of CBM588 in colorectal cancer radical surgery: A single-center, randomized controlled trial. (PubMed, Cell Rep Med) - P4 | "We find that perioperative administration of CBM588 significantly benefits recovery of intestinal function, lowers risk of infectious complications, and enhances systemic immunity by increasing circulating T cells. CBM588 serves as a promising probiotic with favorable tolerability in CRC patients undergoing radical surgery."

Journal • Colorectal Cancer • Gastroenterology • Gastrointestinal Disorder • Oncology • Solid Tumor

Clostridium butyricum enhances cognitive function in APP/PS1 mice by modulating neuropathology and regulating acetic acid levels in the gut microbiota. (PubMed, Microbiol Spectr) - "Our comprehensive evaluation of CBM588 demonstrates its remarkable potential to ameliorate cognitive impairment in APP/PS1 mice by modulating gut microbiota composition, upregulating short-chain fatty acids, particularly acetate, and mitigating neuroinflammation. These findings not only provide novel insights into the gut-brain axis in AD but also offer a promising therapeutic strategy, highlighting the importance of targeting gut microbiota in future AD research and interventions."

IO biomarker • Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • BAX • BCL2 • CLDN1 • IL1B • IL6 • OCLN • TJP1 • TNFA

Adding a Probiotic (CBM588) to Pembrolizumab for the Treatment of Renal Cell Cancer After Surgery (clinicaltrials.gov) - P2 | N=62 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P2 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • CXCL8

Effect of Clostridium butyricum and antibiotics using simultaneous simple suspension in mice with Clostridioides difficile infection. (PubMed, Exp Mol Pathol) - "This study using mice demonstrates the effectiveness of simultaneous simple suspensions of CBM and antibiotics in treating CDI. This approach significantly reduces C. difficile counts, modulates cytokine levels, and maintains probiotic viability, potentially making it a viable option for administration via gastric tubes in clinical settings."

Journal • Preclinical • Infectious Disease • Oncology • IFNG • IL10 • IL6 • TNFA

Combination therapy with levofloxacin and the probiotic Clostridium butyricum MIYAIRI 588 enhances immune checkpoint inhibitor efficacy. (PubMed, Int J Cancer) - "A broad-spectrum antibiotic cocktail (ampicillin, neomycin, vancomycin, and metronidazole) with CBM588 diminished antitumor effects and reduced survival in mice when compared with the control, demonstrating the importance of microbiota-targeted therapeutic combinations. However, while LVFX+CBM588 improved ICI efficacy, it worsened dextran sulfate sodium (DSS)-induced colitis, suggesting immune activation contributes to inflammation. These findings emphasize the potential of customized antibiotic-probiotic combinations in cancer immunotherapy, while also stressing the necessity to manage immune-related adverse effects."

Checkpoint inhibition • Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Oncology

Long-term clinical outcomes with nivolumab/ipilimumab with or without Clostridium butyricum MIYAIRI588 in metastatic renal cell carcinoma (mRCC): A randomized phase Ib clinical trial. (ASCO 2025) - P1 | "Although limited by the sample size, the combination of nivolumab/ipilimumab with CBM588 demonstrated superior clinical activity over nivolumab/ipilimumab in our cohort. Additionally, ORR, PFS and OS with nivo/ipi/CBM588 exceeded those observed with nivolumab and ipilimumab in historical datasets (Motzer et al. NEJM)."

Clinical • Clinical data • Metastases • P1 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

Targeted probiotic therapy in irritable bowel syndrome: a clinical evaluation on Clostridium butyricum CBM588 and Bifidobacterium longum W11. (PubMed, Front Med (Lausanne)) - "Their strain-specific benefits highlight the potential of targeted probiotic strategies in IBS management. Future studies with larger sample sizes and longer follow-up periods are recommended to confirm and expand these findings."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain

The Protective Effects of Lactobacillus reuteri Combined With Clostridium butyricum Miyairi 588 on Intestinal Barrier Function, Water Transport, and Oxidative Stress in a Rat Model of 5FU-Induced Diarrhea. (PubMed, Food Sci Nutr) - "5-Fluorouracil (5FU) is a commonly employed and highly effective chemotherapeutic agent in clinical oncology. LCs also notably diminished the mRNA expression levels of AQP7, VIP, and PKA. This study demonstrates that LCs have therapeutic effects on colitis, primarily through their antioxidant properties, anti-apoptotic effects, mucosal barrier integrity maintenance, neutrophil infiltration reduction, and inflammatory cytokines and aquaporin expression modulation."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Oncology • AKT1 • CASP3 • IFNG • IL1B • NFKB1 • OCLN • TNFA • VCAM1

Irritable Bowel Syndrome with Diarrhea (IBS-D): Effects of Clostridium butyricum CBM588 Probiotic on Gastrointestinal Symptoms, Quality of Life, and Gut Microbiota in a Prospective Real-Life Interventional Study. (PubMed, Microorganisms) - "These findings support the C. butyricum CBM588 probiotic strain as a safe, well-tolerated, and microbiota-targeted intervention for IBS-D. Randomized controlled trials are warranted to confirm efficacy."

HEOR • Journal • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Pain

CBM588 in Improving Clinical Outcomes in Patients Who Have Undergone Donor Hematopoietic Stem Cell Transplant (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Apr 2025 ➔ Mar 2026 | Trial primary completion date: Apr 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Oncology • Transplantation

THE CLINICAL APPLICATION OF CLOSTRIDIUM BUTYRICUM MIYAIRI 588 FOR PATIENTS WITH COLORECTAL ADENOMATOUS POLYPS (DDW 2025) - "Its efficacy in modulating gut microbiota and enhancing intestinal barrier function highlights its clinical relevance. Future research should focus on larger, long-term studies to validate these findings and optimize its role in preventive oncology."

Clinical • Colonic Polyps • Colorectal Cancer • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

Association between circulating B cell subtypes and treatment response in patients with metastatic renal cell carcinoma (mRCC) (AACR 2025) - "This study investigates the prognostic significance of circulating CD5+ B cells in mRCC patients (pts) treated with cabozantinib/nivolumab with or without CBM588, a live bacterial product. This open-label, randomized trial enrolled pts aged ≥18 years with histologically verified advanced or mRCC who had not received prior systemic therapy for metastatic disease... High baseline levels of CD5+ B cells are associated with inferior outcomes in patients with mRCC treated with cabozantinib and nivolumab. These findings suggest that CD5+ B cells may serve as a prognostic biomarker and a potential target to improve ICB outcomes in mRCC."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD5 • IL6

A novel combined immunotherapy of gut microbial metabolite butyrate and oncolytic adenovirus in colorectal cancer (AACR 2025) - "The combination therapy of CBM588 and OBP-702 demonstrated similar synergistic antitumor effects in mouse subcutaneous and rectal tumor models. In conclusion, the combination of OBP-702 and butyrate shows promise as a synergistic antitumor strategy and may represent a novel therapeutic approach for colorectal cancer."

IO biomarker • Oncolytic virus • Colorectal Cancer • Oncology • Solid Tumor • CD8 • CXCL10 • TP53

Prognostic impact of Clostridium butyricum MIYAIRI (CBM588) in combination with pembrolizumab for advanced urothelial carcinoma (AUA 2025) - "All patients had recurrence or progression of UC after receiving cisplatin or carboplatin-based chemotherapy as first treatment. These findings might suggest that the arrangement treatment of gut microbiome using CBM588 has a prognostic impact for advanced UC patients undergoing pembrolizumab."

Combination therapy • Metastases • Gastric Cancer • Gastrointestinal Disorder • Genito-urinary Cancer • Hepatocellular Cancer • Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

CBM588 With Cabozantinib/Nivolumab Shows Promise in Metastatic RCC (Targeted Oncology) - P1 | N=31 | NCT05122546 | "...data from the phase 1 indicate that the addition of CBM588 to cabozantinib and nivolumab significantly improved progression-free survival (PFS) and objective response rate (ORR) in patients with mRCC. However, the study did not demonstrate a significant increase in Bifidobacterium spp., the primary end point, challenging initial hypotheses regarding the mechanism of action."

P1 data • Renal Cell Carcinoma

PROREDI: Study to Evaluate the Treatment Benefits of Probiotic Clostridium Butyricum CBM588® for IBS-D (clinicaltrials.gov) - P=N/A | N=400 | Completed | Sponsor: Liaquat University of Medical & Health Sciences | Trial completion date: Sep 2024 ➔ Mar 2025 | Initiation date: Sep 2023 ➔ Nov 2024 | Trial primary completion date: Mar 2024 ➔ Feb 2025

HEOR • Trial completion date • Trial initiation date • Trial primary completion date • Gastrointestinal Disorder

PROREDI: Study to Evaluate the Treatment Benefits of Probiotic Clostridium Butyricum CBM588® for IBS-D (clinicaltrials.gov) - P=N/A | N=400 | Completed | Sponsor: Liaquat University of Medical & Health Sciences | N=200 ➔ 400

Enrollment change • HEOR • Gastrointestinal Disorder

CBM588 Reduces Colorectal Polyp Recurrence (clinicaltrials.gov) - P=N/A | N=500 | Enrolling by invitation | Sponsor: Kaohsiung Medical University

New trial • Colonic Polyps • Colorectal Cancer

Clostridium Butyricum CBM588® vs. Rifaximin for Symptomatic Uncomplicated Diverticular Disease (SUDD) (clinicaltrials.gov) - P=N/A | N=70 | Completed | Sponsor: Dr. Amjad Khan

New trial • Gastroenterology • Gastrointestinal Disorder