picibanil (OK-432) / Roche - LARVOL DELTA

Simultaneous activation of innate immune suppressive components impairs antitumor efficacy of immunotherapy against the innate immune system (AACR 2024) - "We then employed OK-432, which reportedly stimulates TLR-2, TLR-4, and/or TLR-9, as OK-432 is widely used in Japan in the clinic...Taken together, we propose that successful combination treatment stimulating innate immunity against immunogenically cold cancers requires controlling the unwanted co-activation of innate immune suppressive cells. This study clearly demonstrates the mechanism of acquired resistance after administration of reagents that activate innate immunity, such as TLR agonists or STING agonists, and provides the basis for future successful combination therapy."

Clinical • Oncology • CXCL1 • CXCR2 • TLR4 • TLR9

Radiofrequency hyperthermia enhances the effect of OK-432 for Hepatocellular carcinoma by activating of TLR4-cGAS-STING pathway. (PubMed, Int Immunopharmacol) - "The combined therapy of RFH with OK-432 resulted in a better tumor response, and a prolonged survival compared to the other three treatments. In conclusion, RFH in combination with OK-432 might reduce the residual and recurrent tumor after RFA of large and irregular HCCs, and serve as a new option for other solid malignancies treated by RFA."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • TLR4

Effectiveness of pleurodesis for postoperative air leaks after lung resection. (PubMed, J Cardiothorac Surg) - "The efficacies of autologous blood patch, talc, and OK-432 would be considered comparable and early postoperative pleurodesis could shorten drainage time. Prospective studies are required."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Pleurodesis using OK-432 for persistent pleural effusion after cardiac surgery in the neonatal period or early infancy. (PubMed, Asian Cardiovasc Thorac Ann) - "Pleurodesis using OK-432 is effective and reliable for persistent postoperative pleural effusion in neonates and early infants. Most of the complications, which derived from inflammatory reactions, were temporary and controllable. However, severe lymphedema is difficult to control."

Journal • Pleural effusion • Surgery • Atrial Fibrillation • Cardiovascular • Infectious Disease • Inflammation • Pediatrics • Respiratory Diseases • Septic Shock

PHASE 1B/2 DOSE-EXPANSION, OPEN-LABEL STUDY TO EVALUATE SAFETY AND ANTI-TUMOR ACTIVITY OF INTRAVESICAL INSTILLATION OF TARA-002 IN ADULTS WITH HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER (SUO 2023) - P1b/2 | "TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin and is being developed for the treatment of high-grade NMIBC. TARA-002 is manufactured using the same master cell bank as OK-432, which is approved in Japan and Taiwan for the treatment of several oncology indications...The study duration per subject is 6 months for Cohort A and 24 months for Cohort B. Phase 1b/2 is currently open for enrollment. "

Clinical • P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

ADVANCED-1: PHASE 1A DOSE-FINDING, OPEN-LABEL STUDY TO EVALUATE SAFETY AND TOXICITY OF INTRAVESICAL INSTILLATION OF TARA-002 IN ADULTS WITH HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER (SUO 2023) - "TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin and is being developed for the treatment of high-grade NMIBC via intravesical instillation. TARA-002 is manufactured using the same master cell bank as OK-432, which is approved in Japan and Taiwan for the treatment of several oncology indications... In the ADVANCED-1 study, TARA-002 was generally well tolerated at all three evaluated dose levels and thus demonstrated a favorable safety profile for the treatment of high-grade NMIBC. A MTD was not determined, and dose escalation remains ongoing in exploratory Phase 1a cohorts. Furthermore, anti-tumor activity was observed at 20 KE and 40 KE."

Clinical • Metastases • P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Pain • Solid Tumor

Synergistic Effect of OK-432 in Combination with Anti-PD-1 Antibody for Residual Tumors after Radiofrequency Ablation of Hepatocellular Carcinoma (RSNA 2023) - "The combined therapy of OK-432 with αPD-1 antibody induced a strong anti-tumor immune response, which significantly inhibited the residual tumors after iRFA of HCC. *Clinical Relevance/Application: This concept may provide a new strategy to increase the curative efficacy of RFA for medium-to-large or irregular HCCs."

Combination therapy • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • FOXP3

Elucidation of the Microvascular Embolization Effects of Imipenem/Cilastatin¦ Evaluation at the Level of Microvessels using Monochromatic X-ray in Vivo Study (RSNA 2023) - "A portion of one ear of each rabbit was injected subcutaneously with picibanil (0.5 KE) to create an inflammation-induced model. The characteristics of IPM/CS as an embolic material in vivo were elucidated. In vivo, much larger vessels are embolized than the actual particle size. It was also suggested that the embolization effect duration might differ between normal and inflammation-induced areas."

Preclinical • Anesthesia • Immunology • Inflammation • Pain • Rheumatology

STING Pathway Activation and Antitumor Immunity Induction by an Injectable Hydrogel Loaded Lysed OK-432 and DOX for Incomplete Radiofrequency Ablated Liver Cancer (RSNA 2023) - "*Purpose: To investigate the efficacy and mechanism of an injectable hydrogel loaded lysed OK-432 and doxorubicin for incomplete radiofrequency ablated (inRFA) liver cancer. The novel ROD peptide hydrogel was effective for the treatment of liver cancer previously treated with inRFA. *Clinical Relevance/Application: This modality probably leads to a progression in the eradication of larger liver cancer in clinical practice."

Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • CD4 • CD8 • IFNB1 • IFNG • STING • TNFA

Non-invasive Radiofrequency Hyperthermia Enhances the Effect of OK-432 for Hepatocellular Carcinoma Via Activation of cGAS-STING Pathway (RSNA 2023) - "Furthermore, this combined treatment resulted in a better tumor response and a prolonged survival. In conclusion, the combination therapy might be a new treatment strategy in reducing the residual tumor after RFA of medium-to-large or irregular HCCs, bringing a new option for other types of malignancies treated by RFA."

Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • IFNB1 • TLR4

Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation. (PubMed, J Nanobiotechnology) - "The novel ROD peptide hydrogel induced an antitumor immunity by activating the STING pathway, which was effective for treating residual liver cancer after iRFA of HCC."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • CD4 • CD8 • IFNB1 • IFNG • TNFA

The neural and cardiovascular effects of exposure of gram-positive bacterial inflammation in preterm fetal sheep. (PubMed, J Cereb Blood Flow Metab) - "Picibanil was also associated with acute changes in heart rate and attenuation of the maturational increase in mean arterial pressure. Even a single exposure to a low-dose gram-positive bacterial-mediated inflammation during the antenatal period is associated with prolonged changes in vascular and neural function."

Gram positive • Journal • Cardiovascular • CNS Disorders • Infectious Disease • Inflammation • Solid Tumor • Vascular Neurology

A Case of Intractable Chylorrhea Following Breast Cancer Surgery with a History of Liver Cirrhosis (PubMed, Gan To Kagaku Ryoho) - "Locally injected picibanil solution through the drain on postoperative days 12 and 17 further decreased the drainage to 20 mL/day, and the drain was removed. The patient was discharged on postoperative day 22. The occurrence of chylorrhea was a concern due to the risk of distal hepatic collateral flow, regional lymph nodes and vessels, and high hepatic flow pressure due to liver cirrhosis."

Journal • Surgery • Breast Cancer • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Oncology • Solid Tumor

Synergistic effect of OK-432 in combination with anti-PD-1 antibody for residual tumors after radiofrequency ablation of hepatocellular carcinoma (CIRSE 2023) - No abstract available

Combination therapy • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

A Comparison of the Efficacies of OK-432 and Talc Slurry for Pleurodesis in Patients with Prolonged Air Leak after Pulmonary Resection. (PubMed, Ann Thorac Cardiovasc Surg) - "Pleurodesis with talc may be an effective treatment option for postoperative air leak. Our findings suggest that talc was as effective as OK-432 and resulted in a milder systemic inflammatory response."

Journal • Immunology • Inflammation • Systemic Inflammatory Response Syndrome • CRP

Synergistic effect of OK-432 in combination with an anti-PD-1 antibody for residual tumors after radiofrequency ablation of hepatocellular carcinoma. (PubMed, Biomed Pharmacother) - "The combined therapy of OK-432 with αPD-1 antibody induced a strong antitumor immune response, which significantly inhibited the residual tumors after iRFA of HCC. This concept may provide a new treatment strategy to increase the curative efficacy of RFA for medium-to-large and irregular HCCs."

Combination therapy • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • FOXP3

Efficacy of OK-432 sclerotherapy for different types of lymphangiomas: a review and meta-analysis. (PubMed, Braz J Otorhinolaryngol) - "To our knowledge, our study represents the first meta-analysis examining the efficacy of OK-432 in the treatment of different types of LMs. However, the regional differences and the age differences of the subjects are the main limitations of this study and should be avoided in further research. Our results suggested that OK-432 sclerotherapy for macrocystic lymphangiomas was more effective."

Journal • Retrospective data • Review

Phase 1b/2 dose expansion, open-label study to evaluate safety and anti-tumor activity of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer. (ASCO 2023) - P1, P1a | "TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin...Therefore, nonclinical and clinical evidence with OK-432 and TARA-002 support the ADVANCED-1 study (dose escalation Phase 1a [NCT05085977] and dose expansion Phase 1b/2 [NCT05085990])...Phase 1b/2 is expected to begin enrollment in May 2023. Clinical trial information: NCT05085977; NCT05085990."

Clinical • P1/2 data • Allergy • Bladder Cancer • Genito-urinary Cancer • Immunology • Oncology • Solid Tumor • Urothelial Cancer

Hypertonic glucose pleurodesis for preterm neonates with chylothorax. (PubMed, Pediatr Pulmonol) - "Previously used pleurodesis agents have included talc, minocycline, OK-432, bleomycin, and povidone-iodine. 50% Dextrose (D50) has been reported to be useful for pleurodesis in adults. We successfully managed two cases of prematurely born infants with D50 as an alternative chemical sclerosant for chemical pleurodesis in a resistant chylothorax and discussed evidence of its use in the literature."

Journal • Cardiovascular • Infectious Disease • Respiratory Diseases

Phase 1 Trial Begins Dosing of TARA-002 Cell Therapy for NMIBC (Targeted Oncology) - "'While bladder cancer is the 6th most common cancer in the United States today, with NMIBC representing approximately 80% of diagnoses, treatment options for these patients remain limited,' Edward M. Messing, MD...said in a statement. 'There is an urgent need for new therapeutic interventions for these patients, as there continues to be an increase in recurrence, progression and an escalated number of patients needing cystectomies.'"

Media quote

Phase 1a/b Study of Intravesical Instillation of TARA-002 in Adults with High-grade Non-muscle Invasive Bladder Cancer (AUA 2023) - P1, P1a | "TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin and is being developed for the treatment of high-grade (HG) NMIBC. TARA-002 is manufactured using the same master cell bank as OK-432 (Picibanil ® )... The 1a will establish the RP2D of TARA-002 and 1b will provide further evidence of anti-tumor activity and safety of TARA-002."

Clinical • P1 data • Allergy • Bladder Cancer • Genito-urinary Cancer • Immunology • Oncology • Solid Tumor • Urothelial Cancer

Phase 1a/b Safety Study of Intravesical Instillation of TARA-002 in Adults with High-grade Non-muscle Invasive Bladder Cancer (ADVANCED-1) (SUO 2022) - "TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin. TARA-002 is manufactured using the same master cell bank as OK-432 (Picibanil ® )...Phase 1a is currently open for enrollment. "

Clinical • P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Evaluation of the Effects of Polidocanol Injection in the Treatment of Temporomandibular Joint Hypermobility - A Prospective Study. (PubMed, Ann Maxillofac Surg) - "Sclerosing agents have been used for temporomandibular joint (TMJ) hypermobility since decades, some of which are ethanolamine oleate, and OK-432, sodium psylliate (sylnasol), but there are no studies on the usage of polidocanol - a well-known sclerosing agent which does not have much side effects and is inexpensive. Overall, a success rate of 86.6% (13/15) was encountered at the end of three months, with seven patients not reporting any further episodes of dislocation after one injection and six patients not reporting any episode of dislocation after two injections. Polidocanol sclerotherapy can be used as a treatment modality for chronic recurrent dislocation of the TMJ, rather than opting for more invasive procedures for the same."

Journal • Musculoskeletal Diseases • Pain • Rheumatology

Interstitial Lung Disease after OK-432 Pleurodesis for Malignant Pleural Effusion in Breast Cancer-A Case Report (PubMed, Gan To Kagaku Ryoho) - "After 4 courses of capecitabine therapy for right chest wall recurrence of breast cancer, ER(+, 10-15%), PgR(-), HER2(-), she underwent pleurodesis using OK-432 for increased right pleural effusion. Drug- induced lung injury by pleurodesis carries the risk of delaying resumption of chemotherapy. We report this case with a review of the literature."

Journal • Pleural effusion • Breast Cancer • HER2 Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

Association between malformation type, location and functional deficits in lymphatic malformations of the head and neck in children. (PubMed, Eur Arch Otorhinolaryngol) - "There is an association between malformation type, location according to de Serres and CDS in children with LM of the head and neck. Patients with microcystic and mixed malformations in stage V had lowest CDS levels."

Journal • Pediatrics