- |||||||||| Amnolake (tamibarotene) / Syros
Trial completion date, Trial primary completion date, Combination therapy: SELECT-AML-1: Tamibarotene Plus Venetoclax/Azacitidine in Participants with Newly Diagnosed AML (clinicaltrials.gov) - Feb 22, 2024
P2, N=95, Recruiting,
Our study comprehensively analyzed the toxicity profiles of anti-GD2 monoclonal antibodies and provides an important reference for clinical monitoring and ADR identification of these drugs. Trial completion date: Apr 2024 --> Apr 2028 | Trial primary completion date: Apr 2024 --> Apr 2028
- |||||||||| nanvuranlat (JPH203) - J / Pharma, Ohara Pharma
Targeting the Amino Acid Transporter SLC7A5 for Pulmonary Fibrosis (San Diego Convention Center, Room 7A-B (Upper Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_7168;
In summary, our results have revealed a novel molecular and metabolic pathway(s) modulating fibrosis resolution and would be a promising cell selective therapy for IPF targeting cellular metabolism. Research Funding: NHLBI (R56HL158549 and R01HL167732 for M. C)
- |||||||||| Unituxin (dinutuximab) / United Therapeutics Corp, Ohara Pharma
Trial primary completion date, Combination therapy: STING: NK Cells Infusions With Irinotecan, Temozolomide, and Dinutuximab (clinicaltrials.gov) - Feb 15, 2024
P1/2, N=31, Recruiting,
Research Funding: NHLBI (R56HL158549 and R01HL167732 for M. C) Trial primary completion date: Dec 2023 --> Dec 2024
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor, Amnolake (tamibarotene) / Syros
Review, Journal: Retinoid Therapy for Neuroblastoma: Historical Overview, Regulatory Challenges, and Prospects. (Pubmed Central) - Feb 10, 2024
To promote isotretinoin use in Japan as a treatment for neuroblastoma, our clinical research team is planning to launch an investigator-initiated, registration-directed clinical trial. The present review article discusses the basic science behind retinoid therapy, pre-clinical/clinical evidence on neuroblastoma, the concept of the proposed clinical trial, and prospects for this therapy.
- |||||||||| foscenvivint (PRI724) / PRISM Pharma, Ohara Pharma
Journal: C-X-C chemokine receptor type 4 promotes tubular cell senescence and renal fibrosis through ?-catenin-inhibited fatty acid oxidation. (Pubmed Central) - Feb 8, 2024
In this study, we adopted adriamycin nephropathy and 5/6 nephrectomy models, and cultured tubular cell line...To inhibit ?-catenin by ICG-001, an inhibitor of ?-catenin, could significantly block CXCR4-suppressed fatty acid oxidation...CXCR4 promotes tubular cell senescence and renal fibrosis by inducing ?-catenin and inhibiting fatty acid metabolism. Our findings provide a new theory for tubular cell injury in renal fibrosis.
- |||||||||| foscenvivint (PRI724) / PRISM Pharma, Ohara Pharma, XAV-939 / Novartis
Journal: ?-catenin mediates growth defects induced by centrosome loss in a subset of APC mutant colorectal cancer independently of p53. (Pubmed Central) - Feb 7, 2024
Consistent with this notion, ?-catenin inhibition using XAV939 or ICG-001 partially prevented centrinone-induced death and rescued the growth two APC-mutant organoid lines tested. Our study reveals a novel role for canonical WNT signaling in regulating centrosome loss-induced growth defect/death in a subset of APC-mutant colorectal cancer independently of the classical p53 pathway.
- |||||||||| humanised dinutuximab (Hu14.18K322A) / Essential Pharma
Trial completion date, Metastases: Therapy for Children With Advanced Stage Neuroblastoma (clinicaltrials.gov) - Jan 16, 2024
P2, N=153, Active, not recruiting,
Active, not recruiting --> Completed Trial completion date: Dec 2023 --> Dec 2024
- |||||||||| Nypta (tideglusib) / ASD Therap, Amnolake (tamibarotene) / Syros
Journal: Cocktail Cell-Reprogrammed Hydrogel Microspheres Achieving Scarless Hair Follicle Regeneration. (Pubmed Central) - Jan 16, 2024
In vitro and in vivo studies show that AHFS can regulate fibroblast fate, induce fibroblast-to-DPC reprogramming by activating the PI3K/AKT pathway, finally promoting wound healing and in situ HF regeneration while inhibiting scar formation in a two-pronged translational approach. In conclusion, AHFS provides a new and effective strategy for functional repair of skin wounds.
- |||||||||| foscenvivint (PRI724) / PRISM Pharma, Ohara Pharma
Journal: The E156K mutation in the CRYAA gene affects the epithelial-mesenchymal transition and migration of human lens epithelial cells. (Pubmed Central) - Jan 8, 2024
Cells transfected with E156K-mutated CRYAA expressed remarkably higher levels of the mesenchymal biomarkers N-cadherin and vimentin but decreased levels of the epithelial biomarker E-cadherin, whereas opposite trends were observed in cells treated with the ?-catenin inhibitor, ICG001...E156K-mutated CRYAA induced EMT, in which the HLECs lost cell polarity, and acquired a mesenchymal phenotype with greater migratory capability. These biological effects may be associated with activation of the Wnt/?-Catenin and FAK/Src signaling pathways.
- |||||||||| Unituxin (dinutuximab) / United Therapeutics Corp, Ohara Pharma
Review, Journal: Safety and efficacy of dinutuximab in the treatment of neuroblastoma: A review. (Pubmed Central) - Dec 20, 2023
Recent studies on relapsed and refractory NB have shown the potential efficacy of dinutuximab. Further research is required to properly incorporate Dinutuximab in current treatment modalities.
- |||||||||| Amnolake (tamibarotene) / Syros, Nippon Shinyaku, Zeria Pharma, RaQualia, Ohara Pharma
Journal, Combination therapy: Use of tamibarotene, a potent and selective RAR? agonist, in combination with azacitidine in patients with relapsed and refractory AML with RARA gene overexpression. (Pubmed Central) - Dec 18, 2023
P2
Further research is required to properly incorporate Dinutuximab in current treatment modalities. In 21 response-evaluable patients, the complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rate was 19%, and median time to initial CR/CRi was 1.2
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, nanvuranlat (JPH203) - J / Pharma, Ohara Pharma
Journal: GPRC5C Drives Branched-Chain Amino Acid Metabolism in Leukemogenesis. (Pubmed Central) - Dec 17, 2023
This anti-leukemia effect was strengthened in the presence of venetoclax and azacitidine. Our results indicate that the GPRC5C-NF-?B-SLC7A5-BCAAs axis is a therapeutic target that can compromise leukemia stem cell function in AML.
- |||||||||| Anktiva (inbakicept) / ImmunityBio
IL15 (N-803) and IL21 (oHSV-21) Significantly Enhance ROR1 CAR NK Cells Against Pediatric Neuroblastoma () - Dec 11, 2023 - Abstract #TCTASTCTCIBMTR2024TCT_ASTCT_CIBMTR_1267;
The N-803 combined with dinutuximab and exPBNK cells significantly extended the survival of NB xenografts (Chu/Cairo, et al, JITC...C021 was generated by modifying C134 to express human IL21 gene... Our data demonstrated IL15 or IL21 based novel cytokine therapy (N-803 or C021) significantly enhanced the anti-tumor efficacy of ROR1 CAR NK targeting NB in vitro and in vivo (Funded by U54 CA232561).
- |||||||||| Unituxin (dinutuximab) / United Therapeutics Corp, Ohara Pharma, NKTR-255 / Nektar Therap
Targeting Ewing Sarcoma By Genetically and Epigenetically Modified Ex-Vivo Expanded NK Cells in Combination with NKTR-255 and Dinutuximab (221 (Meeting Level, Henry B. Gonzalez Convention Center); in-person) - Dec 11, 2023 - Abstract #TCTASTCTCIBMTR2024TCT_ASTCT_CIBMTR_739;
Conclusions Our data demonstrated enhanced anti-tumor efficacy of modified NK (IL1RAP CAR NK, TGF?i-NK, IL1RAP CAR CXCR2 NK) cells alone and combined with NKTR-255 and dinutuximab against ES in vitro. This provided a rationale for a preclinical evaluation of the anti-tumor effects of these modified NK cells combined with NKTR-255 and dinutuximab in vivo.
- |||||||||| E7386 / Eisai, PRISM Pharma
Journal: E7386 is not a Specific CBP/?-Catenin Antagonist. (Pubmed Central) - Nov 27, 2023
Clinical trial information: UMIN000034080. It can thus be concluded that E7386 is not a specific CBP/?-catenin antagonist.
- |||||||||| foscenvivint (PRI724) / PRISM Pharma, Ohara Pharma
Journal: Inhibiting CBP Decreases AR Expression and Inhibits Proliferation in Benign Prostate Epithelial Cells. (Pubmed Central) - Nov 25, 2023
Then, we used ICG-001 and shRNA to inhibit CBP in prostate epithelial cells (BPH-1 cells and RWPE-1 cells), and conducted immunofluorescence, cell viability assay, flow cytometry analysis, and Western blot to analyze the effects of CBP on AR expression and proliferation in prostate epithelial cells...(4) Inhibiting CBP decreases AR expression and inhibits proliferation in benign prostate epithelial cells. CBP may be a potential target to affect AR expression and the proliferation of prostate epithelial cells in BPH.
- |||||||||| foscenvivint (PRI724) / PRISM Pharma, Ohara Pharma
Journal: Differential Kat3 Coactivator Usage Regulates Brain Metabolism and Neuronal Differentiation. (Pubmed Central) - Nov 21, 2023
CBP may be a potential target to affect AR expression and the proliferation of prostate epithelial cells in BPH. Rebalancing the equilibrium between CBP/?-catenin versus p300/?-catenin associated transcription, utilizing the small molecule CBP/beta-catenin antagonist ICG-001, enhances mitochondrial oxidative phosphorylation, metabolic function, and neuronal differentiation and may be able to ameliorate the cognitive decline seen in neurodegenerative disorders, including Alzheimer's Disease.
- |||||||||| foscenvivint (PRI724) / PRISM Pharma, Ohara Pharma
Preclinical, Journal: Inhibition of Wnt/?-catenin signaling reduces renal fibrosis in murine glycogen storage disease type Ia. (Pubmed Central) - Nov 13, 2023
Treating GSD-Ia mice with a CBP/?-catenin inhibitor, ICG-001, significantly decreased nuclear translocated active ?-catenin and reduced renal levels of renin, Snail1, ?-SMA, and collagen-IV. The results suggest that inhibition of Wnt/?-catenin signaling may be a promising therapeutic strategy for GSD-Ia nephropathy.
- |||||||||| Oncogenetic-Driven Targeted Therapy for Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia : A French ALL-Target Observatory Report (Grand Hyatt - Grand Hall B) - Nov 3, 2023 - Abstract #ASH2023ASH_3168;
P
In relapse/refractory (R/R) patients, standard of care treatments, including nelarabine, yield response rate of about 20-40% and responses are of short duration...For example, TTOs included Tofacitinib and Venetoclax (Tofa/Ven) in case of IL7R (CD127) expression or IL7R-pathway alterations (IL7R ALT ), 5-azacytidine and Venetoclax (Aza/Ven) in case of T-ALL/LL with epigenetic regulators alterations (DNMT3A, ASXL1, PHF6, TET2, PRC2, IDH1/2, SRSF2...) or Temsirolimus, Erwinase and Venetoclax (Tem/Erw/Ven) in case of PI3K signaling pathway alterations (PI3K ALT )...Twenty-five patients received a TTO, including 14 Aza/Ven (56%), 8 Tofa/Ven (32%), 2 Tem/Erw/Ven (8%) and 1 Trametinib/Ven (4%)...A better knowledge of the oncogenetic landscape of T-ALL, and a close collaboration between clinicians and biologists, resulted in individualized treatment strategies. With a 3 months cumulative incidence of response of 70%, TTOs appear to be a promising approach in R/R T-ALL.
- |||||||||| foscenvivint (PRI724) / PRISM Pharma, Ohara Pharma
The Transcription Factors NFATc1 and NFATc2 Control Glucocorticoid Resistance in Pediatric T-Cell Acute Lymphoblastic Leukemia (Grand Hyatt - Grand Hall B) - Nov 3, 2023 - Abstract #ASH2023ASH_3032;
In agreement, NFATc1 or NFATc2 specific gene silencing in 3 T-ALL GC resistant cell line models and primary cells increases dexamethasone response, by restoring GR canonical transcriptional activity through the increase expression of BIM GR target gene (p value <0.05). Overall, we revealed for the first time the involvement of NFATc1 and NFATc2 transcription factors in supporting GC resistance in T-ALL cells by the modulation of cholesterol biosynthesis and Wnt/
- |||||||||| Alecensa (alectinib) / Roche
Journal: A Combination of Alectinib and DNA-Demethylating Agents Synergistically Inhibits Anaplastic-Lymphoma-Kinase-Positive Anaplastic Large-Cell Lymphoma Cell Proliferation. (Pubmed Central) - Oct 28, 2023
Crizotinib and alectinib are first- and second-generation ALK TKIs, respectively, approved for the treatment of ALK-positive ALCL (ALK ALCL) and ALK NSCLC...Thus, to improve the clinical outcomes of ALK ALCL therapy, we investigated the synergistic efficacy of the combination of alectinib and the DNA-demethylating agent azacytidine, decitabine, or OR-2100 (an orally bioavailable decitabine derivative)...The combination of alectinib and OR-2100 markedly altered gene expression in ALCL cells, including that of genes implicated in apoptotic signaling, which possibly contributed to the synergistic anti-ALCL effects of this drug combination. Therefore, alectinib and OR-2100 combination therapy has the potential to improve the outcomes of patients with ALK ALCL.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Amnolake (tamibarotene) / Syros
Enrollment change, Trial completion date, Trial initiation date, Trial withdrawal, Trial primary completion date, Combination therapy: Phase I/II Study of SY-1425 (Tamibarotene) in Combination With Azacitidine and Venetoclax for Patients With Chronic Myelomonocytic Leukemia (clinicaltrials.gov) - Oct 25, 2023
P1/2, N=0, Withdrawn,
Active, not recruiting --> Completed Not yet recruiting --> Withdrawn | N=52 --> 0 | Trial completion date: Jan 2030 --> Oct 2023 | Initiation date: Mar 2024 --> Sep 2023 | Trial primary completion date: Jan 2028 --> Oct 2023
- |||||||||| peretinoin (K-333) / Kowa, Bay11-7082 / Bayer, Amnolake (tamibarotene) / Syros, Nippon Shinyaku, Zeria Pharma, RaQualia, Ohara Pharma
Preclinical, Journal: Acyclic retinoid peretinoin reduces hemorrhage-associated brain injury in vitro and in vivo. (Pubmed Central) - Oct 22, 2023
Not yet recruiting --> Withdrawn | N=52 --> 0 | Trial completion date: Jan 2030 --> Oct 2023 | Initiation date: Mar 2024 --> Sep 2023 | Trial primary completion date: Jan 2028 --> Oct 2023 On the other hand, nuclear factor-?B (NF-?B) inhibitors such as pyrrolidine dithiocarbamate (50
- |||||||||| Unituxin (dinutuximab) / United Therapeutics Corp, Ohara Pharma
Trial completion date, Trial primary completion date: NANT 2013-01: Immunotherapy of Relapsed Refractory Neuroblastoma With Expanded NK Cells (clinicaltrials.gov) - Oct 16, 2023
P1, N=13, Active, not recruiting,
On the other hand, nuclear factor-?B (NF-?B) inhibitors such as pyrrolidine dithiocarbamate (50 Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024
- |||||||||| Unituxin (dinutuximab) / United Therapeutics Corp, Ohara Pharma
Journal: A Multi-Color Flow Cytometric Assay for Quantifying Dinutuximab Binding to Neuroblastoma Cells in Tumor, Bone Marrow, and Blood. (Pubmed Central) - Oct 14, 2023
As the most common clinical samples available for relapsed neuroblastoma are bone marrow aspirates, we developed a method to quantify dinutuximab binding density and the frequency of neuroblastoma cells positive for the antibody in bone marrow aspirates. Here, we describe a multi-color flow cytometry assay that employs non-GD2 antibodies to identify neuroblastoma cells in a mixed population (tumor, bone marrow, or blood) and an anti-GD2 antibody to quantify both the frequency and density of GD2 expression on neuroblastoma cells.
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