- |||||||||| azeliragon (TTP488) / Cantex Pharma
A phase I/II open label study to assess safety and preliminary evidence of a therapeutic effect of azeliragon in patients refractory to first-line treatment of metastatic pancreatic cancer. (Hall A; Poster Bd #: 176a) - Apr 24, 2024 - Abstract #ASCO2024ASCO_3941; P1/2 RAGE interaction with its ligands, including S100 proteins and HMGB1 released from PDAC cells, promotes PDAC invasion, metastasis, and resistance to 5 FU and Gemcitabine...Secondary endpoints include disease control, overall survival, changes in pain as determined by the Brief Pain Inventory, and changes in ECOG performance status, weight, and serum albumin. The study received regulatory approval and accrual started in June 2023.
- |||||||||| Herceptin (trastuzumab) / Roche, azeliragon (TTP488) / Cantex Pharma, Perjeta (pertuzumab) / Roche
RAGE inhibition to decrease cancer therapy related cardiotoxicity in women with early breast cancer (RAGE). (Hall A; Poster Bd #: 207a) - Apr 24, 2024 - Abstract #ASCO2024ASCO_1347; P1/2 In Cohort 4, 6 patients will receive dose dense doxorubicin and cyclophosphamide (ddAC)...As of 2/1/24, 4 patients have been enrolled, with 4 undergoing screening. At the completion of this trial, we plan a randomized trial to evaluate the role of TTP488 to decrease cardiotoxicity, cancer related cognitive decline and disease recurrence.
- |||||||||| azeliragon (TTP488) / Cantex Pharma
Journal: Macrophage RAGE activation is proinflammatory in NASH. (Pubmed Central) - Jan 4, 2024 FFC mice that received a pharmacological inhibitor of RAGE (TTP488), and myeloid-specific RAGE KO mice (RAGE-MKO) had attenuated liver injury associated with a reduced accumulation of RAGE+ recruited macrophages...Correspondingly, the secretome of ligand-stimulated bone marrow derived macrophages from RAGE-MKO mice had an attenuated capacity to activate CD8+ T cells. Our data implicate RAGE as what we propose to be a novel and potentially targetable mediator of the proinflammatory signaling of recruited macrophages in NASH.
- |||||||||| azeliragon (TTP488) / Cantex Pharma
Enrollment open, Trial initiation date: Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma (clinicaltrials.gov) - Sep 15, 2023 P1/2, N=18, Recruiting, Our data implicate RAGE as what we propose to be a novel and potentially targetable mediator of the proinflammatory signaling of recruited macrophages in NASH. Not yet recruiting --> Recruiting | Initiation date: Mar 2023 --> Sep 2023
- |||||||||| azeliragon (TTP488) / Cantex Pharma
Journal: RAGE inhibitor TTP488 (Azeliragon) suppresses metastasis in triple-negative breast cancer. (Pubmed Central) - Jul 14, 2023 These results show that TTP488 impairs metastasis of TNBC and further clarifies the signaling and cellular mechanisms through which RAGE mediates metastasis. Importantly, as TTP488 displays a favorable safety profile in human studies, our study provides the rationale for evaluating TTP488 in clinical trials to treat or prevent metastatic TNBC.
- |||||||||| azeliragon (TTP488) / Cantex Pharma
Review, Journal: RAGE Inhibitors in Neurodegenerative Diseases. (Pubmed Central) - May 16, 2023 Some of the RAGE antagonists, such as Azeliragon, are currently in clinical development for treating neurological diseases, including AD, although currently there have been no FDA-approved therapeutics based on the RAGE antagonists. This review outlines the AGE-RAGE interactions as a leading cause of the onset of neurological diseases and the current efforts on developing therapeutics for neurological diseases based on the RAGE antagonists.
- |||||||||| azeliragon (TTP488) / Cantex Pharma
RAGE EXPRESSING MACROPHAGE SUBSETS MEDIATE INFLAMMATION IN NASH (South Hall A, Poster Hall - McCormick Place) - Mar 23, 2023 - Abstract #DDW2023DDW_1520; FFC-RLMC-KO and RAGE-i mice had significant attenuation of liver injury compared to FFC-WT and vehicle treated controls respectively, assessed by NAS-grading and ALT. Further, RLMC-KO mice had significantly lower RAGE expression by IHC of liver sections and fibrosis compared to FFC fed WT-mice.
- |||||||||| Enrollment open, Trial completion date, Trial primary completion date: RAGE Inhibition to Decrease Cardiotoxicity in Women With Early Breast Cancer (clinicaltrials.gov) - Jan 9, 2023
P1/2, N=48, Recruiting, Further, RLMC-KO mice had significantly lower RAGE expression by IHC of liver sections and fibrosis compared to FFC fed WT-mice. Not yet recruiting --> Recruiting | Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Nov 2023 --> Nov 2024
- |||||||||| Trial initiation date, Metastases: RAGE Inhibition to Decrease Cardiotoxicity in Women With Early Breast Cancer (clinicaltrials.gov) - Sep 29, 2022
P1/2, N=48, Not yet recruiting, Importantly, as TTP488 displays a high safety profile in human trials, this study provides the rationale for evaluating TTP488 in clinical trials to treat or prevent metastatic breast cancer. Initiation date: Aug 2022 --> Nov 2022
- |||||||||| azeliragon (TTP488) / vTv Therapeutics
Journal: Design, synthesis and anti-TNBC activity of Azeliragon triazole analogues. (Pubmed Central) - Jan 19, 2022 In order to develop a new anti-TNBC agent, we designed, synthesized and screened 26 Azeliragon triazole analogues to determine their anti-TNBC activities in vitro. The most active compound was KC-10 with an IC value of 0.220 ± 0.034 μM.
- |||||||||| Cilcane (cilengitide) / Iceni Pharma, azeliragon (TTP488) / vTv Therapeutics
Journal: RAGE and αVβ3-integrin are essential for suPAR signaling in podocytes. (Pubmed Central) - Nov 17, 2021 The magnitude of this inhibition was indistinguishable from the effect produced by a neutralizing antibody against suPAR. These data suggest that orally bioavailable small molecule RAGE antagonists could represent a useful therapeutic strategy for a wide range of clinical conditions associated with elevated serum suPAR, including primary FSGS and AKI.
- |||||||||| azeliragon (TTP488) / vTv Therapeutics
[VIRTUAL] RAGE DEPENDENT IRF SIGNALING IN MACROPHAGES IS PROINFLAMMATORY IN MOUSE AND HUMAN NASH () - Oct 21, 2021 - Abstract #AASLD2021AASLD_2045; In a diet induced mouse model of NASH, recruited macrophages repopulated the resident macrophage niche, and mediate liver inflammation via RAGE dependent upregulation of IRF5 and IRF7 and downstream inflammatory cytokine production. Our data implicate RAGE signaling as a novel and potentially targetable mediator of the proinflammatory phenotype of recruited macrophages in NASH .
- |||||||||| azeliragon (TTP488) / vTv Therapeutics
Journal: TTP488 ameliorates NLRP3-associated inflammation, viability, apoptosis, and ROS production in an Alzheimer's disease cell model by mediating the JAK1/STAT3/NFκB/IRF3 pathway. (Pubmed Central) - Jul 10, 2021 Use of WP1160, a STAT3 agonist, re-activated the downstream STAT3/NFκB/IRF3 pathway and NLRP3 expression. Moreover, we found that WP1160 counteracted the role of TTP488 in Aβ-induced SH-SY5Y cells' viability, inflammation, apoptosis, and ROS production.
- |||||||||| azeliragon (TTP488) / vTv Therapeutics
Review, Journal: Alzheimer's disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links. (Pubmed Central) - Jun 30, 2021 In this context, the hyperphosphorylation of tau and the formation of neurofibrillary tangles have been associated with the dysfunction of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in the nervous tissues as well as the decrease in the expression of GLUT-1 and GLUT-3 in the different areas of the brain, increase in reactive oxygen species, and production of mitochondrial alterations that occur in T2DM. These findings have contributed to the implementation of overlapping pharmacological interventions based on the use of insulin and antidiabetic drugs, or, more recently, azeliragon, amylin, among others, which have shown possible beneficial effects in diabetic patients diagnosed with AD.
- |||||||||| azeliragon (TTP488) / vTv Therapeutics
[VIRTUAL] SAFETY AND EFFICACY RESULTS FROM THE PHASE 2 ELEVAGE STUDY OF AZELIRAGON IN MILD ALZHEIMER’S DISEASE AND TYPE 2 DIABETES (On Demand Symposia D) - Feb 19, 2021 - Abstract #ADPD2021ADPD_1583; Consistent with previous studies, azeliragon was generally well‐ tolerated with similar incidences of treatment‐emergent adverse events overall and by system organ class (SOC) in both treatment groups. Conclusions The study failed to meet its primary objective with no statistically significant treatment differences on the ADAS‐cog14 primary endpoint. Results for primary and secondary efficacy outcome measures, as well as safety measures, will be presented.
- |||||||||| azeliragon (TTP488) / Cantex Pharma
Trial termination, Trial primary completion date: Study of Azeliragon in Patients With Mild Alzheimer's Disease and Impaired Glucose Tolerance (clinicaltrials.gov) - Feb 2, 2021 P2, N=43, Terminated, Results for primary and secondary efficacy outcome measures, as well as safety measures, will be presented. Active, not recruiting --> Terminated | Trial primary completion date: Apr 2020 --> Dec 2020; for business reasons
- |||||||||| azeliragon (TTP488) / Cantex Pharma
Trial completion date, Trial primary completion date: Study of Azeliragon in Patients With Mild Alzheimer's Disease and Impaired Glucose Tolerance (clinicaltrials.gov) - Jan 5, 2021 P2, N=43, Active, not recruiting, Active, not recruiting --> Terminated | Trial primary completion date: Apr 2020 --> Dec 2020; for business reasons Trial completion date: Jul 2023 --> Feb 2021 | Trial primary completion date: Apr 2023 --> Apr 2020
- |||||||||| azeliragon (TTP488) / vTv Therapeutics
Journal: High mobility group box 1 protein regulates osteoclastogenesis through direct actions on osteocytes and osteoclasts in vitro. (Pubmed Central) - Sep 17, 2020 In bone marrow macrophages (BMMs), toll-like receptor 4 (TLR4) inhibition with LPS-RS, but not receptor for advanced glycation end products (RAGE) inhibition with Azeliragon attenuated osteoclast differentiation...Our findings also suggest that increased osteoclastogenesis induced by apoptotic osteocytes CM is not mediated through HMGB1/RAGE activation and that direct HMGB1 actions in osteocytes stimulate pro-osteoclastogenic signal release from Cx43 osteocytes. Based on these findings, we propose that HMGB1 exerts dual effects on osteoclasts, directly by inducing differentiation through TLR4 and RAGE activation and indirectly by increasing pro-osteoclastogenic cytokine secretion from osteocytes.
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