FZD5

Pioneering AI technology successfully designs antibodies de novo for six therapeutic targets, including one without an experimentally resolved structure SEOUL, South Korea, March 17, 2025 /PRNewswire/ -- Galux Inc., a South Korean startup specializing in AI-driven protein therapeutics design, has published a study showcasing the capabilities of its AI platform, GaluxDesign, in de novo antibody design. This research marks an important milestone in AI-driven antibody discovery, demonstrating the successful design of antibodies against six distinct therapeutic targets, including a target without an experimentally resolved structure. Continue Reading A graphical representation verifying the binding strength between the antibodies designed by GaluxDesign and each therapeutic target. "De novo antibody design has been one of the major challenges in AI-based drug discovery, requiring atomic-level precision to ensure specific binding to target epitopes," said Chaok Seok, CEO of Galux. "A few previously reported cases of de novo antibody design have shown only limited success, particularly in terms of target diversity and binding affinity. Our findings prove that AI can reliably generate novel antibodies with high precision, specificity, and sensitivity across diverse therapeutic targets." A graphical representation verifying the binding strength between the antibodies designed by GaluxDesign and each therapeutic target. The study presents an AI-driven approach to de novo antibody design. The team identified binders from a yeast display single-chain variable fragment (scFv) library comprising approximately one million designed antibody sequences, followed by screening binders against a target protein. Binders with varying binding strengths were identified for six targets, including PD-L1, HER2, EGFR(S468R), ACVR2A/B, FZD7, and ALK7. Notably, the team successfully designed antibodies targeting ALK7, a protein without an experimentally resolved structure, as well as antibodies targeting a novel epitope of FZD7 discriminating subtypes FZD1 and FZD5. This highlights the platform's broad applicability for novel antibody discovery. The designed PD-L1 targeting antibody showed outstanding binding affinity (KD=9.0pM) and developability comparable to the commercial therapeutic antibody Atezolizumab. Additionally, antibodies designed for EGFR(S468R) displayed exceptional specificity, precisely distinguishing the mutant from wild-type EGFR based on a single amino acid difference, which is an essential feature for minimizing off-target effects in early-stage drug development. "This study underscores the potential of AI-driven antibody design and its broad applicability in antibody discovery," added Seok. "By continuously advancing our AI platform with a deep understanding of atomic-level protein interactions, we aim to transform therapeutic drug discovery, improving both efficiency and success rates." The full research paper is available here: About Galux With over 25 years of expertise in the field, Galux is pioneering AI-powered protein design with its proprietary platform, GaluxDesign, which enables precise de novo protein design and engineering. GaluxDesign has been developed to deeply understand the physical principles that govern protein folding and interactions. This approach enables the platform to tackle various protein design challenges including epitope-specific antibody design. Since its incorporation in 2020, the company has raised USD 18 million from reputable investors, including InterVest, Pathway Partners, DAYLI Partners, LG Corp., and KDB Capital. SOURCE Galux WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Researchers have found a way to better control the preclinical generation of key neurons depleted in Parkinson's disease, pointing toward a new approach for a disease with no cure and few effective treatments. Researchers at the University of Toronto have found a way to better control the preclinical generation of key neurons depleted in Parkinson's disease, pointing toward a new approach for a disease with no cure and few effective treatments. The researchers used an antibody to selectively activate a receptor in a molecular signaling pathway to develop dopaminergic neurons. These neurons produce dopamine, a neurotransmitter critical to brain health. Researchers around the world have been working to coax stem cells to differentiate into dopaminergic neurons, to replace those lost in patients living with Parkinson's disease. But efforts have been hindered in part by an inability to target specific receptors and areas of the brain. "We used synthetic antibodies that we had previously developed to target the Wnt signaling pathway," said Stephane Angers, principal investigator on the study and director of the Donnelly Centre for Cellular and Molecular Biology. "We can selectively activate this pathway to direct stem cells in the midbrain to develop into neurons by targeting specific receptors in the pathway," said Angers, who is also a professor in the Leslie Dan Faculty of Pharmacy and the Temerty Faculty of Medicine, and holds the Charles H. Best Chair of Medical Research at U of T. "This activation method has not been explored before." The study was recently published in the journal Development. Parkinson's disease is the second-most common neurological disorder after Alzheimer's, affecting over 100,000 Canadians. It particularly impacts older men, progressively impairing movement and causing pain as well as sleep and mental health issues. Most previous research efforts to activate the Wnt signaling pathway have relied on a GSK3 enzyme inhibitor. This method involves multiple signaling pathways for stem cell proliferation and differentiation, which can lead to unintended effects on the newly produced neurons and activation of off-target cells. "We developed an efficient method for stimulating stem cell differentiation to produce neural cells in the midbrain," said Andy Yang, first author on the study and a PhD student at the Donnelly Centre. "Moreover, cells activated via the FZD5 receptor closely resemble dopaminergic neurons of natural origin." Another promising finding of the study was that implanting the artificially-produced neurons in a rodent model with Parkinson's disease led to improvement of the rodent's locomotive impairment. "Our next step would be to continue using rodent or other suitable models to compare the outcomes of activating the FZD5 receptor and inhibiting GSK3," said Yang. "These experiments will confirm which method is more effective in improving symptoms of Parkinson's disease ahead of clinical trials." This research was supported by the University of Toronto Medicine by Design program, which receives funding from the Canada First Research Excellence Fund, and the Canadian Institutes of Health Research.

Bispecific antibodies (bsAbs) possess unique advantages due to their ability to simultaneously target two distinct antigens, which helps to enhance the immune system's recognition and killing of tumor cells. As of the end of 2023, 14 bsAbs have been approved: 11 of them for cancer treatment and 3 for non-oncological indications. BsAbs come in various structural formats, target different antigens, and mediate antitumor functions through different molecular mechanisms. The development of antibodies targeting G protein-coupled receptor (GPCR) targets is relatively more challenging compared to traditional drugs such as small molecules, peptides, recombinant hormones, etc., with slower progress in comparison. In contrast, the development of Antibody-Drug Conjugates (ADCs) targeting members of the GPCR family has seen a gradual increase in research momentum over the past decade. Dual-specificity antibodies related to GPCRAccording to statistics from the Synapse database, there are currently 23 bispecific antibody therapeutics worldwide targeting GPCR (G protein-coupled receptor) class targets, including targets such as CXCR4 (+PD-L1) , GPRC5D (+CD3) , GPRC5D (+BCMA+CD30) , SSTR2 (+CD3) , ETA (+CD3) , ETA (+TGF-B) , CCR8 (+TIGIT) , CCR8 (+CTLA4) , CCR2 (+M-CSF) , FZD5 (+LRP6) , FZD4 (+LRP5), GIPR+GLP-1R, FSHR (+albumin) , LGR5 (+EGFR). Johnson & Johnson's Talquetamab became the world's first approved bispecific antibody targeting a GPCR class target to be marketed. Bispecific antibodies that target both GPRC5D and CD3 include Nanjing Leads Biolabs' LBL-034, which is in Phase 1/2 clinical trials, and Roche's Forimtamig, which is in Phase 1 clinical development. Additionally, the GPRC5D+CD3+BCMA trispecific antibody MBS314, co-developed by Kyinno Biotechnology and Beijing Mabworks Biotech, is in Phase 1/2 clinical trials, and the GPRC5D+CD3+BCMA trispecific antibody SIM-0500, co-developed by Simcere Pharmaceutical Group Limited and Shanghai Xianxiang Pharmaceutical Technology, is in the clinical application stage. Translate the following text into English with professional accuracy: The Dutch biotechnology company Merus has developed a bispecific product, Petosemtamab (MCLA-158), currently in Phase 1/2 clinical trials. This is a bispecific Biclonics® fucose-low full human IgG1 antibody that simultaneously targets the epidermal growth factor receptor (EGFR) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5). Petosemtamab is designed with three independent mechanisms of action: Inhibition of the EGFR-dependent signaling pathway: By binding with EGFR on the surface of tumor cells, it blocks normal signal transmission, thereby inhibiting processes such as tumor cell proliferation, migration, and angiogenesis.  LGR5-mediated EGFR internalization and degradation: Petosemtamab can bind to LGR5, leading to the internalization and degradation of EGFR within cancer cells, further diminishing EGFR’s pro-carcinogenic activity.  Enhancement of antibody-dependent cellular cytotoxicity and phagocytosis (ADCC/ADCP): With its bispecific structure, Petosemtamab can recruit and activate the immune system's natural killer (NK) cells and macrophages, enhancing their ability to recognize and eliminate cancer cells expressing EGFR and LGR5, thus achieving indirect antitumor effects. At the 2023 Annual Meeting of the American Association for Cancer Research (AACR), Merus presented the results of a Phase 1/2 clinical trial cohort expansion, showing that Petosemtamab demonstrated a manageable safety profile and significant therapeutic effects in patients with advanced head and neck squamous cell carcinoma (HNSCC). Among the 43 patients with advanced HNSCC treated with Petosemtamab, the overall response rate (ORR) reached 37.2%, with tumor reductions observed in 16 patients. The data specifics included: 1 patient achieved a complete response (CR), and 15 patients had partial responses (PR). In addition, 15 patients achieved a stable disease (SD) condition. As a result, the disease control rate (DCR) was 72.1% (n=31/43; 95% CI, 56.3%-84.7%), which means that over seventy percent of the patients experienced no tumor progression or saw reductions in tumor size following treatment. The bi-specific product SZN-1326, originally developed by the American biotechnology company Surrozen, is in Phase 1 clinical research. The product is designed based on Surrozen's proprietary SWAP™ technology, with the goal of modulating the Wnt signaling pathway in intestinal epithelium. The Wnt/β-catenin signaling pathway plays a crucial role in the renewal of intestinal stem cells, the maintenance of intestinal epithelial homeostasis, and the regeneration process. Studies have confirmed that this pathway is dysregulated in inflammatory bowel disease (IBD). Fzd5 is a Wnt receptor with high expression in intestinal epithelial tissues. SZN-1326 is a bi-specific, effectorless IgG1 antibody that targets both FZD5 and 8, as well as the LRP6 receptor. Preclinical research has indicated that SZN-1326 can effectively activate the Wnt signaling pathway. Furthermore, in organoid cultures of the intestine, it can stimulate the growth of the organoids; it increases the expression levels of the Wnt target gene Axin2 in colonic tissue; and in a mouse model, SZN-1326 can also ameliorate colitis symptoms induced by Dextran Sulfate Sodium (DSS). At present, bispecific antibodies targeting GPCR class targets are primarily indicated for cancer-related clinical applications, with popular therapeutic directions including multiple myeloma, plasma cell myeloma, solid tumors, and more. However, there is also a diversity of clinical indications, such as bispecific antibodies targeting GIPR and GLP-1R for the treatment of obesity and diabetes, bispecific antibodies targeting ETA for the treatment of pulmonary fibrosis and pulmonary arterial hypertension, bispecific antibodies targeting FSHR for the treatment of male/female infertility, and bispecific antibodies targeting FZD4 for the treatment of diabetic retinopathy and wet age-related macular degeneration.