- |||||||||| Aramchol (aramchol meglumine) / Galmed
POTENTIAL USE OF IPSC-DERIVED HEPATOCYTE-LIKE CELLS TO DEVELOP PRECISION MEDICINE FOR ASH () - Oct 15, 2024 - Abstract #AASLD2024AASLD_2156;
In vitro exposure of iHLCs to ethanol induced lipid accumulation and upregulated fatty acid synthesis pathways. iHLCs were also generated from ASH patients' blood samples and their further characterization may facilitate the development of precision therapeutics.
- |||||||||| Adakveo (crizanlizumab-tmca) / Novartis, Opdivo (nivolumab) / Ono Pharma, BMS
P-selectin as an emerging target for the treatment of primary and secondary brain tumors (Section 3) - Mar 5, 2024 - Abstract #AACR2024AACR_6905;
P2
As such, it has the potential to reduce tumor burden and improve patient outcomes. This work can improve our understanding of GAMs function, which may pave the way for new and effective treatments for primary and secondary brain tumors.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Journal: Modeling T cell temporal response to cancer immunotherapy rationalizes development of combinatorial treatment protocols. (Pubmed Central) - Mar 2, 2024
We demonstrate that combining anti-PD-1 therapy with anti-4-1BB agonist enhances the recruitment and proliferation of activated precursors, resulting in tumor control. These data suggest that effective response to anti-PD-1 therapy is dependent on sufficient influx of activated precursor CD8+ cells to the TME and highlight the importance of understanding system-level dynamics in optimizing immunotherapies.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Preclinical, Journal, Tumor mutational burden, BRCA Biomarker, PARP Biomarker, PD(L)-1 Biomarker, IO biomarker: Spectrum of Response to Platinum and PARP Inhibitors in Germline BRCA-Associated Pancreatic Cancer in the Clinical and Preclinical Setting. (Pubmed Central) - Aug 7, 2023
Anti-PD-1 attenuated tumor growth in a novel humanized glBRCA PDAC PDX model...Additional treatment options for this unique subpopulation are needed. We generated model systems in PDXs and an ex vivo system (EVOC) that faithfully recapitulate these specific clinical scenarios as a platform to investigate the mechanisms of resistance for further drug development.
- |||||||||| Review, Journal: An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH. (Pubmed Central) - Jul 18, 2023
Extrahepatic inflammatory signals from the circulation, adipose tissue or gut are targets of hormonal agonists (semaglutide, tirzepatide, FGF19/FGF21 analogues), microbiota or lifestyle interventions...In advanced fibrosis, cell therapy with restorative macrophages or reprogrammed T-cells (e.g., CAR T) may accelerate repair through HSC deactivation or killing, or by enhancing matrix degradation. Heterogeneity of disease - either due to genetics or divergent disease drivers - is an obstacle to defining effective drugs for all patients with NASH that will be incrementally overcome.
- |||||||||| anti-PD-L1 antibody / Tikcro Technologies
PD-L1 blockade therapeutic effect in Tau P301S (line PS19) mouse model of tauopathy (In-Person) - Jul 6, 2023 - Abstract #AAIC2023AAIC_8186;
Methods : Tau P301S mice were treated with anti-PD-L1 antibody, or isotype control, and tested for the functional effect of the treatment on parameters of cognitive performance and brain pathology, at different time points after treatment...Conclusions : PD-L1 blockade evokes an immune response that leads to functional improvement on cognitive performance and reduced brain pathology in Tau P301S mice. These findings, taken together with our previous reports of anti-PD-L1 therapeutic effect in other AD or tauopathy mouse models, substantiate the generalization of this treatment approach - targeting the peripheral immune system in order to drive brain tissue repair in neurodegenerative conditions.
- |||||||||| Bridging the gap - (Poster Area) - Apr 12, 2023 - Abstract #EASLILC2023EASL_ILC_694;
Recently we validated our advanced MPS NASH model using two anti-NASH compounds, Obeticholic acid and Elafibranor...Selonsertib showed no antifibrotic or anti-inflammatory effects in our MPS NASH model at clinically relevant dosage, matching results from phase III STELLAR trials, despite reduced fibrosis and inflammation being detected in alternative 3D spheroid models. Overall, we demonstrate how this NASH liver MPS provides translatable insights into drug efficacy for NASH therapeutics and brings a promising, sensitive alternative for pre-clinical NASH screening to help fast-track decision making and access to the market.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Journal, Tumor-Infiltrating Lymphocyte: An activation to memory differentiation trajectory of tumor-infiltrating lymphocytes informs metastatic melanoma outcomes. (Pubmed Central) - May 17, 2022
Trajectory analysis of single-cell melanoma CD8 TILs also identified a high fraction of memory/resident memory-scoring TILs in anti-PD-1 responders, which expanded post therapy...Late/persistent, but not early activation signatures, prognosticate melanoma survival, and co-express with dendritic cell and IFN-γ response programs. These data identify an activation-like state associated to poor response and suggest successful memory conversion, above resuscitation of exhaustion, is an under-appreciated aspect of successful anti-tumoral immunity.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Biomarker, Journal, Checkpoint inhibition, Tumor microenvironment: The interaction of CD4 helper T cells with dendritic cells shapes the tumor microenvironment and immune checkpoint blockade response. (Pubmed Central) - Apr 20, 2022
Reconstitution of Tht cells in vitro and in an ovalbumin-specific αβ TCR CD4 T-cell mouse model, shows that the Tht program is primed in tumor-draining lymph nodes by dendritic cells presenting tumor antigens, and that their function is important for harnessing the antitumor response of anti-PD-1 treatment. Our molecular and functional findings support the modulation of Tht-dendritic cell interaction checkpoints as a major interventional strategy in immunotherapy.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Journal, Checkpoint inhibition, PD(L)-1 Biomarker, IO biomarker: Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors. (Pubmed Central) - Apr 15, 2022
We further find that inhibiting purine synthesis increases pyrimidine to purine ratio, elevates expression of the immunoproteasome and significantly enhances the response of autologous primary CD8 T cells to anti-PD-1. These results suggest that treating patients with high-ASS1 cancers with purine synthesis inhibition is beneficial and may also sensitize them to immune checkpoint inhibition therapy.
- |||||||||| Aramchol (arachidyl amido cholanoic acid) / Galmed, Weizmann Institute of Science
Higher daily Aramchol dose results in higher effect size in fibrosis improvement in the ARMOR study open label part (Poster Area) - Mar 16, 2022 - Abstract #EASLILC2022EASL_ILC_1125;
Data is corroborated by congruent changes in fibrosis biomarkers and by a biochemical response in aminotransferases. The data presented here, albeit preliminary, is aligned with the hypothesis that higher Aramchol exposure results in an improved efficacy profile and a direct anti-fibrotic effect may be manifested as early as 24 weeks.
- |||||||||| Aramchol (arachidyl amido cholanoic acid) / Galmed, Weizmann Institute of Science
HIGHER DAILY ARAMCHOL DOSE RESULTS IN HIGHER EFFECT SIZE IN FIBROSIS IMPROVEMENT IN THE ARMOR STUDY OPEN LABEL PART () - Mar 3, 2022 - Abstract #NASHTAG2022NASH_TAG_97;
Data is corroborated by congruent changes in fibrosis biomarkers and by a biochemical response in aminotransferases. The data presented here, albeit preliminary, is aligned with the hypothesis that higher Aramchol exposure results in an improved efficacy profile and that a direct anti-fibrotic effect may be manifested as early as 24 weeks.
- |||||||||| Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Clinical, Review, Journal: Non-Alcoholic Steatohepatitis (NASH) - A Review of a Crowded Clinical Landscape, Driven by a Complex Disease. (Pubmed Central) - Feb 2, 2022
At the time of writing this review, only Zydus Cadila's new drug application for Saroglitazar had been approved (2020) for NASH therapy in India...Obeticholic acid (Intercept Pharmaceuticals), Cenicriviroc (Allergan), Aramchol (Galmed Pharmaceuticals), Resmetirom (Madrigal Pharmaceuticals), Dapagliflozin and Semaglutide (Novo Nordisk) are in advanced Phase 3 clinical trials, while Belapectin (Galectin Therapeutics), MSDC-0602K (Cirius Therapeutics), Lanifibranor (Inventiva), Efruxifermin (Akero) and Tesamorelin (Theratechnologies) are expected to start Phase 3 trials soon...Hence, the development of a single therapy for NASH seems challenging and unlikely, despite the plethora of later stage trials due to report. We therefore predict that clinical, patient and company interest in pipeline and next-generation therapies will remain high for some time to come.
- |||||||||| anti-PD-L1 antibody / Tikcro Technologies
Preclinical, Journal, PD(L)-1 Biomarker, IO biomarker: Key role of the CCR2-CCL2 axis in disease modification in a mouse model of tauopathy. (Pubmed Central) - Jan 11, 2022
The CCR2/CCL2 axis is required to modify pathology using PD-L1 blockade in a mouse model of tauopathy. This modification involves, in addition to monocytes, the accumulation of FOXP3 regulatory CD4 T cells in the brain, and the T-cell chemoattractant, Cxcl12.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Journal: Targeting Pin1 renders pancreatic cancer eradicable by synergizing with immunochemotherapy. (Pubmed Central) - Jan 5, 2022
Mechanistically, Pin1 drives the desmoplastic and immunosuppressive TME by acting on CAFs and induces lysosomal degradation of the PD-1 ligand PD-L1 and the gemcitabine transporter ENT1 in cancer cells, besides activating multiple cancer pathways. Thus, Pin1 inhibition simultaneously blocks multiple cancer pathways, disrupts the desmoplastic and immunosuppressive TME, and upregulates PD-L1 and ENT1, rendering PDAC eradicable by immunochemotherapy.
- |||||||||| Review, Journal: Emerging Therapies for the Treatment of Non-Alcoholic Steatohepatitis: A Systematic Review. (Pubmed Central) - Dec 25, 2021
Thus, Pin1 inhibition simultaneously blocks multiple cancer pathways, disrupts the desmoplastic and immunosuppressive TME, and upregulates PD-L1 and ENT1, rendering PDAC eradicable by immunochemotherapy. These novel agents may fill a pharmacotherapy gap in patients with NASH and possibly prevent progression to advanced liver disease.
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Journal, PD(L)-1 Biomarker, IO biomarker: NASH limits anti-tumour surveillance in immunotherapy-treated HCC. (Pubmed Central) - Dec 16, 2021
When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8PD1CXCR6, TOX, and TNF T cells...Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment.
- |||||||||| Aramchol (arachidyl amido cholanoic acid) / Galmed, Weizmann Institute of Science
Clinical, P2b data, Journal: Aramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial. (Pubmed Central) - Nov 17, 2021
P2b
Early termination due to adverse events (AEs) was <5%, and Aramchol 600 and 400 mg were safe, well tolerated and without imbalance in serious or severe AEs between arms. Although the primary end point of a reduction in liver fat did not meet the prespecified significance level with Aramchol 600 mg, the observed safety and changes in liver histology and enzymes provide a rationale for SCD1 modulation as a promising therapy for NASH and fibrosis and are being evaluated in an ongoing phase 3 program.
- |||||||||| Aramchol (arachidyl amido cholanoic acid) / Galmed, Weizmann Institute of Science, resmetirom (MGL-3196) / Madrigal Pharma, lanifibranor (IVA337) / Inventiva
[VIRTUAL] PHYSICIAN AWARENESS OF AND PREFERENCES FOR COMBINATION THERAPY FOR NAFLD/NASH TREATMENT () - Oct 21, 2021 - Abstract #AASLD2021AASLD_2152;
Nevertheless, the stages of NAFLD/NASH suggest that treating multiple facets of the disease may be required . Hepatologists appear more aware and accepting than gastroenterologists of the potential for combination therapy in NAFLD/NASH .
- |||||||||| Egrifta (tesamorelin acetate) / Theratechnologies, Massachusetts General Hospital, Aramchol (arachidyl amido cholanoic acid) / Galmed, Weizmann Institute of Science
[VIRTUAL] TREATMENT OF HUMAN IMMUNODEFICIENCY VIRUS- ASSOCIATED NON-ALCOHOLIC FATTY LIVER DISEASE – A SYSTEMATIC REVIEW () - Oct 21, 2021 - Abstract #AASLD2021AASLD_2116;
The available data suggest improvement in liver fat content as measured by MRI-PDFF with Tesamorelin . Given the prevalence, risk factors, and inability to generalize data to the HIV population, more studies need to be done for patients with HIV-associated NAFLD .
- |||||||||| anti-PD-1 antibody / Tikcro Technologies
Characterization of molecular and spatial diversity of macrophages in hepatocellular carcinoma (Poster Hall) - Oct 1, 2021 - Abstract #SITC2021SITC_528;
P2
Our analysis of resected tumor from anti-PD-1 treated patients, will allow us to correlate MF programs, and direct T cell interaction, with clinical response, and will inform therapeutic trials targeting specific MF populations so as to improve clinical efficacy of cancer immunotherapy. Trial Registration NCT03916627
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