Agonistic antibodies bind to specific receptors on cells and mimic the action of the natural ligand of that receptor, thereby activating signaling pathways and eliciting cellular responses. Unlike traditional antibodies, which are often used to block or neutralize the activity of their target molecules (acting as antagonists), antibody agonists actively stimulate a biological response. Recently, more studies are delving into the mechanisms and therapeutic potential of these antibody agonists.
Last week, a paper was published describing how antibody agonists trigger immune receptor signaling through local exclusion of receptor-type protein tyrosine phosphatases. By extending the kinetic-segregation (KS) model, the researchers hypothesized that the key immune receptor in T cells is regulated by a balance between kinases and phosphatases. The findings establish a framework for developing new and improved therapies for autoimmunity and cancer.
Just last month, researchers illustrated an engineering approach inspired by a naturally occurring Fab-Fab homotypic interaction which allows for i-shaped antibody (iAb) engineering. This would enable the tuning of agonist antibody function and provide a framework for the development of intrinsic antibody agonists with the potential for generalization across broad receptor classes. The results from this paper showed potent intrinsic agonism of five tumor necrosis factor receptor superfamily (TNFRSF) targets with the engineered iAbs.
Recently, several clinical trials with antibody agonists also show promising results for therapeutic use. From preclinical studies, ADG106, a ligand-blocking agonistic antibody targeting CD137, demonstrated tumor suppression in various animal models and a manageable safety profile with preliminary anti-tumor efficacy in patients with advanced cancers. Meanwhile, results from a Phase II trial of the CD40 agonistic antibody sotigalimab in combination with nivolumab in subjects with anti-PD-1-resistant metastatic melanoma revealed a favorable safety profile consistent with the toxicity profiles of each agent.
This report aims to explore the events and trends of the biopharmaceutical industry in Q2 (April, May, June). Besides crovalimab and Vyloy, two more novel antibody drugs have been approved this year
These past few weeks, several antibody drug startups have progressed from the pre-seed stage to final funding rounds. In the pre-seed stage, the focus is on early research, often funded by founders, grants, or angel investors. As the company progresses to the seed stage, it seeks additional funding to validate its scientific concept and develop initial prototypes, attracting early-stage venture capital.
In August, the US FDA approved Galderma’s Nemluvio (nemolizumab) for adult patients living with prurigo nodularis (PN). Nemluvio is the first approved monoclonal antibody specifically inhibiting the signaling of IL-31, a neuroimmune cytokine that drives multiple disease mechanisms in (PN). Prurigo nodularis is a chronic skin condition that affects approximately 181,000 patients in the United States
Anti-drug antibodies (ADAs) are immune system proteins that can develop in response to therapeutic drugs, particularly biologics like monoclonal antibodies. These biopharmaceuticals have significantly advanced therapies for cancer and autoimmune diseases, but their long-term use can elicit immunogenicity due to repeated administration. The host immune system may recognize epitopes in the biologic drug as foreign, triggering the production of ADAs. This can lead to the formation of drug–ADA immune complexes, which accelerate drug clearance and potentially neutralize the drug's efficacy.
