SIGLEC1

PatSnap Synapse, a novel, AI Powered Drug Competitive Intelligence database. Access to drugs, clinical trials, patents, literature and news in one search. Palleon Pharmaceuticals, a biopharmaceutical company focused on developing therapies for neoplasms, has presented initial results from the GLIMMER-01 clinical trial for E-602, the first-ever glyco-immune checkpoint inhibitor. This drug is an enzyme that stimulates T lymphocytes and is being developed as a potential treatment for neoplasms. In the Phase 1 trial, E-602 was was found to be well tolerated across the entire dose range evaluated with no dose limiting toxicities. Having met pre-specified gating criteria based on safety and pharmacodynamic activity, Palleon announced plans to proceed with Phase 2 evaluation. Phase 2 studies will evaluate clinical activity of E-602 monotherapy in patients with lung cancer and melanoma. E-602 is a promising drug being developed by Palleon Pharmaceuticals, Inc. It falls under the category of enzyme drugs and works by stimulating T lymphocytes. Its primary therapeutic focus is on neoplasms, and it is currently being tested in Phase 1/2 clinical trials for its effectiveness against neoplasms. Palleon Pharmaceuticals is the originator and active organization behind this innovative drug. Palleon Pharmaceuticals, Inc. was founded in 2016 and is headquartered in Massachusetts, United States. The company is listed on NASDAQ under the symbol MDGL and is focused on developing therapies for neoplasms using fusion protein and enzyme technologies. Their most frequently developed targets include HER2, PDL1, and SIGLEC1. In summary, the initial results from the GLIMMER-01 trial for E-602, a glyco-immune checkpoint inhibitor developed by Palleon Pharmaceuticals, show promise as a potential treatment for neoplasms. The company's focus on developing therapies for neoplasms using fusion protein and enzyme technologies could lead to innovative treatments for patients in the future.

Researchers have identified a receptor, CD169 (also called Siglec1), that is exclusively expressed on macrophages and contributes to the hyper-inflammatory response of macrophages upon infection with SARS-CoV-2. These findings, they believe, may provide an explanation of how SARS-CoV-2 infection of macrophages in lungs of COVID-19 patients promote inflammatory responses. Dysregulation of macrophages during SARS-CoV-2 infection and the over-exuberant production of pro-inflammatory cytokines by these macrophages has been hypothesized to contribute to severity of COVID-19 disease. However, the mechanisms that contribute to the hyper-inflammatory response of macrophages has remained unclear. Now, researchers from Boston University Chobanian & Avedisian School of Medicine have identified a receptor, CD169 (also called Siglec1), that is exclusively expressed on macrophages and contributes to the hyper-inflammatory response of macrophages upon infection with SARS-CoV-2. These findings, they believe, may provide an explanation of how SARS-CoV-2 infection of macrophages in lungs of COVID-19 patients promote inflammatory responses. "These macrophages do not express ACE2, the SARS-CoV-2 receptor. Rather SARS-CoV-2 entry in macrophages was facilitated by a lectin, CD169, which recognizes the spike protein of SARS-CoV-2," explained corresponding author Suryaram Gummuluru, PhD, professor of microbiology. To test their theory, the researchers compared human macrophages that expressed CD169 and those that did not, and then exposed these cells to SARS-CoV-2. "We found that macrophages expressing CD169 were highly permissive for viral entry and initiation of virus replication, but completion of the viral life cycle was blocked and prevented production of new infectious virus particles. Surprisingly, initiation of virus replication and expression of abortive viral transcripts in CD169+ macrophages, was sufficient to activate host surveillance mechanisms (innate immune response) and induce expression of pro-inflammatory responses," said Gummuluru. The researchers hypothesize that persistent activation of viral sensing mechanisms that detect these viral replication intermediates in macrophages might contribute to aberrant inflammation associated with severe COVID-19 disease. According to the researchers, future studies are needed to address the molecular details of this unique virus entry mechanism and the restricted virus replication in macrophages, and how this entry mechanism differs from the conventional ACE2-mediated entry pathway. "Importantly, consideration of therapies that target this alternative virus entry mechanism are needed, as they might prove useful in ameliorating the harmful effects of SARS-CoV-2 infection in macrophages," he adds. These findings appear online in the journal in PLoS Pathogens. Funding for this study was provided by NIH grants R01AI064099 1041 (SG), R01DA051889 (SG), R01AG060890 (SG), P30AI042853 (SG), R01CA2 27292 1042 (ST), R01AI106036 (YB and ST), R01AI133486 (EM), and R21AI135912 (EM) as well 1043 as Fast Grants (EM) and Evergrande MassCPR (EM).