Proactive’s Post

In business news, Biogen and Human Immunology Biosciences (HI-Bio™), a privately-held clinical-stage biotechnology company focused on targeted therapies for patients with severe immune-mediated diseases, announced the companies have entered into a definitive agreement under which Biogen has agreed to acquire HI-Bio for $1.15 billion upfront and up to $650 million in potential milestone payments. HI-Bio’s lead asset, felzartamab, is a fully human anti-CD38 monoclonal antibody that has been shown in clinical studies to selectively deplete CD38+ cells including plasma cells and natural killer, or NK, cells which may allow for additional applications that improve clinical outcomes in a broad range of immune-mediated diseases. https://lnkd.in/eGKCc7kk

Sanofi rides the waves of small molecule #drugdiscovery with a $700M deal with Belharra Therapeutics! This partnership includes $40M upfront to leverage Belharra’s chemoproteomics platform, aiming to target the undruggable in immunology. 💡 Insight - Sanofi's strategic focus on immunology aligns with its vision to become an "immunoscience powerhouse." This collaboration could unlock new therapeutic avenues in #immunology and #inflammation. 🤔 Key questions - What potential breakthroughs can emerge from this partnership? How will Belharra's innovative platform impact the future of immunology drug discovery?

📃Scientific paper: 3-Bromo-Isoxazoline Derivatives Inhibit GAPDH Enzyme in PDAC Cells Triggering Autophagy and Apoptotic Cell Death Abstract: SIMPLE SUMMARY: Cancer cells largely use glycolysis to obtain both chemical energy (ATP) and metabolic intermediates for anabolic reactions, and several studies proved that the blockage of the glycolytic pathway is an efficient anticancer strategy. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key tetrameric glycolytic enzyme, has raised considerable attention in recent years as a potential drug target in pathological conditions in which glycolytic flux has a crucial role. In cancers, a recognized involvement of the Warburg effect, as a key mechanism for cancer-cell energetic metabolism, favouring tumour progression and invasion, has contributed to highlight human GAPDH (hGAPDH) as an effective drug target to specifically hit cancer cells exhibiting metabolic dependence on glycolysis, without significantly affecting normal cells. In this study, we tested the effects of 3-bromo-isoxazoline derivatives specifically designed to bind and inhibit GAPDH activity, in pancreatic ductal-adenocarcinoma cells. ABSTRACT: A growing interest in the study of aerobic glycolysis as a key pathway for cancer-cell energetic metabolism, favouring tumour progression and invasion, has led to consider GAPDH as an effective drug target to specifically hit cancer cells. In this study, we have investigated a panel of 3-bromo-isoxazoline derivatives based on previously identified inhibitors of Plasmodium falciparum GAPDH (PfGAPDH). The compounds are active, to a different extent, as inhibi... Continued on ES/IODE ➡️ https://etcse.fr/U9QoN ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

Geneos Therapeutics‘s personalized #CancerVaccine GNOS-PV02 shows antitumor responses in patients with #HepatocellularCarcinoma (#HCC) Study setting - Phase I/IIa study in 36 patients with #HCC - Patients with Barcelona Cancer Liver Score of B or C refractory to locoregional therapy - Received TKIs while personalized #CancerVaccine was being manufactured - Recieved GNOS-PV02 along with Merck Group’s Keytruda and an Interleukin - 12 adjuvant from INOVIO Pharmaceuticals, Inc. Outcomes Response to therapy - 11 participants completed treatment - 25 discontinued due to progression of disease - 8 partially responded, 3 showed complete response - 8 showed complete molecular response by ctDNA Safety findings - 27 had low-grade had treatment-related adverse events - 3 had immune-related adverse events Immune-related findings - 4 patients of whom 1 had a complete response had more active CD4+ and CD8+ T-cells - Induction of new T-cell responses to the vaccine along with peripheral T-cell receptor expansion Overall survival data is still awaited but it is safe to say that the clinical development of #CancerVaccine GNOS-PV02 will likely progress in the near future

The innate immune system remains an untapped target for a range of indications with high unmet need, from challenging solid tumors to infectious and inflammatory disease. As a result, the STING/TLR agonist landscape is evolving rapidly into immune stimulating antibody conjugates, combination approaches & new immune system targets to tackle the notorious challenge of striking the safety/efficacy balance within innate immunotherapy. As more complex modalities including ADCs and vaccines dominate the preclinical setting, with many key players striving towards agents with stable physical properties to enable delivery systemically, learning from past mistakes before entering the clinic is crucial. 🔔 Register by THIS FRIDAY, May 24 to save up to $350! 🔔 In 4 WEEKS TIME, the 5th Annual STING & TLR Targeted Therapies Summit returns crucially to unpick the lessons of the past year and finally unleash the well-recognised potential of innate immunotherapy. Join us in San Diego to dig into recent successes and clinical failures, bridge the notoriously tricky translational gap by focusing on effective uses of biomarkers and translational modelling, and learn about new approaches and how to enhance combinations with checkpoint inhibitors, plus so much more! Hear from Regeneron, Bolt Biotherapeutics, Inc. , Tallac Therapeutics, Eisai US, TriSalus Life Sciences, Eikon Therapeutics, Merck, OncoNano Medicine, Inc., AbbVie, GeneQuantum Healthcare (Suzhou) Co., Ltd, GSK, Indaptus Therapeutics, Inc. and more! Find out more & register here: https://ter.li/7mpdxy

This new Nature article looks so exciting to us. This paper demonstrates that, as the title indicates, obesity induces PD-1 on macrophages to suppress anti-tumour immunity. The corresponding author of this interesting paper is Prof. Jeffrey Rathmell at Vanderbilt University. Chinese Antibody Society is an independent non-profit, non-government global professional organization with focus upon antibody-based therapeutics. Our society’s official journal, Antibody Therapeutics (2023 CiteScore: 8.7), is an international peer-reviewed, open access journal published by Oxford University Press. You are welcome to visit the official website of the journal (see link below) and submit your therapeutic antibody related manuscripts to our journal. https://lnkd.in/gsTu_U2 #antibodies #antibody #antibodytherapeutics #mabs #mab #biologics

Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets. Modulating protein lipidation potentially offers a unique opportunity to target undruggable oncoproteins through the control of their membrane association, trafficking, protein stability and protein–protein interactions. S-palmitoylation represents the deepest well of untapped opportunities for drug discovery targeting protein lipidation. Emerging reports suggest that palmitoylation offers a unique approach to modulate cancer immunity, microenvironment and oncogenic signaling, with the flexibility to target either S-palmitoylation (ZDHHCs) or diacylation (APTs) owing to the reversibility of this PTM, or to target the site of S-palmitoylation directly, as in the case of TEAD inhibitors. Oncoproteins including NRAS, KRAS4A, HRAS, EGFR and p53 rely on S-palmitoylation cycles for the regulation of their localization, activity or interactors, and >150 oncoproteins are known to be S-palmitoylated. In this review Tate and colleagues have discussed recent advances in identifying targetable protein lipidation pathways in cancer, the current state-of-the-art in drug discovery, and the status of ongoing clinical trials, which have the potential to deliver novel oncology therapeutics targeting protein lipidation. Interesting to see prominent examples of protein lipidation-modulating drugs, drug candidates and tool molecules. #cancerresearch #therapeutictarget #drugdiscovery #smallmolecules #PTMs #cellsignaling #carcinogenesis #NRAS #MAPK #YAP #TEAD #WNT #EGFR #lungcancer #nsclc #PDL1 #tumormicroenvironment # https://lnkd.in/g5nutaGE

https://lnkd.in/g-dnFzwX 🚨 New publication : Cisplatin-Induced Metabolic Responses Measured with Raman Spectroscopy in Cancer Cells, Spheroids, and Canine-Derived Organoids Siddhant Kothadiya, Gabriel Cutshaw, Saji Uthaman, Nora Hassan, Dipak Kumar Sahoo, Hannah Wickham, Elizabeth Quam, Karin Allenspach, Jonathan P. Mochel, Rizia Bardhan Abstract : Ex vivo assessment of drug response with conventional cell viability assays remains the standard practice for guiding initial therapeutic choices. However, such ensemble approaches fail to capture heterogeneities in treatment response and cannot identify early markers of response. Here, we leverage Raman spectroscopy (RS) as an accurate, low-cost, extraction-free, and label-free approach to track metabolic changes in cancer cells, spheroids, and organoids in response to cisplatin treatment. We identified 12 statistically significant metabolites in cells and 19 metabolites in spheroids and organoids as a function of depth. We show that the cisplatin treatment of 4T1 cells and spheroids results in a shift in metabolite levels; metabolites including nucleic acids such as DNA, 783 cm–1 with p = 0.00021 for cells; p = 0.02173 for spheroids, major amino acids such as threonine, 1338 cm–1 with p = 0.00045 for cells; p = 0.01022 for spheroids, proteins such as amide III, 1248 cm–1 with p = 0.00606 for cells; p = 0.00511 for spheroids serve as early predictors of response. Our RS findings were also applicable to canine-derived organoids, showing spatial variations in metabolic changes as a function of organoid depth in response to cisplatin. Further, the metabolic pathways such as tricarboxylic acid (TCA)/citric acid cycle and glyoxylate and dicarboxylate metabolism that drive drug response showed significant differences based on organoid depth, replicating the heterogeneous treatment response seen in solid tumors where there is a difference from the periphery to the tumor core. Our study showcases the versatility of RS as a predictive tool for treatment response applicable from cells to organotypic cultures, that has the potential to decrease animal burden and readout time for preclinical drug efficacy.

AbbVie announced today the acquisition of Celsius Therapeutics, Inc. ("Celsius"), a privately held biotechnology company pioneering new therapies for patients with inflammatory disease. Celsius' lead investigational asset is CEL383, a potential first-in-class anti-TREM1 antibody that has completed a Phase 1 clinical study for the treatment of IBD. TREM1 has been identified as a key disease driver gene in IBD, where it is expressed on inflammatory monocytes and neutrophils. In these cell types and others, TREM1 is upstream of multiple known inflammatory pathways and acts as an amplifier of inflammation. "Given the potential relevance of TREM1 as a key driver of inflammation and pathology in IBD and other conditions, we are eager to advance the development of CEL383 with a goal of helping more patients with IBD achieve remission," said Kori Wallace, MDPhD, vice president, global head of immunology clinical development, AbbVie. "AbbVie shares our excitement about the potential of TREM1 inhibition for patients with inflammatory disease," said Tariq Kassum, M.D., chief executive officer, Celsius. "I'd like to thank the Celsius team for their relentless efforts in the discovery of CEL383. We look forward to the further development of this promising program, which we hope will offer a new approach to the treatment of IBD." Under the terms of the agreement, AbbVie has acquired all outstanding Celsius equity for $250 million in cash, subject to certain customary adjustments. #inflammatorydisease #immunology #IBD #acquisition #AbbVie #CelsiusTherapeutics

Published this week: Check out the 2024 New Drug Modalities Report, which explores the incredible expansion of opportunity over this past year. The #biopharma industry is witnessing a wave of innovation, with new drug modalities projected to reach a pipeline value of $168 billion by 2024, up 14% since 2023. Breakthrough therapies such as #gene therapies, #microbiomes, and expanded #mRNA uses are leading this growth, but investor caution around ADCs and CAR-T remains. The report offers key insights into how companies are adapting to these changes and positioning for future success. Congrats especially to my colleagues, Lu Chen & Brian Bush, who co-authored the work! Explore the full report to learn more: #Biopharma #antibodies #cagt #genetherapy #GLP1 #BCG