Ribosome Newsletter: Navigating the Convergence of Proteomics, AI, Synthetic Biology, and Translational Medicine
Welcome to the latest edition of Ribosome. This week features a new plasma test for early cancer detection, insights into Alzheimer's biomarkers, and the impact of proteomics on COVID-19 vaccine efficacy. Additionally, we highlight recent pharmaceutical mergers and collaborations, including major acquisitions by Merck, Johnson & Johnson, GSK, and Novartis, and a notable AI-driven drug discovery partnership between Alphabet's Isomorphic Labs, Eli Lilly, and Novartis. Join us as we navigate these vital innovations that are reshaping healthcare and pharmaceutical landscapes.
Biomarker Discovery
*Oncology
This study developed a novel proteomics-based plasma test for early detection of multiple cancers, utilizing plasma samples from 440 individuals to measure over 3000 proteins. The test demonstrated high accuracy in detecting early-stage cancers and identifying their tissue of origin, with distinct sex-specific protein panels achieving remarkable sensitivity and specificity. The research offers a promising approach for population-wide cancer screening, emphasizing the potential of proteomic analysis in transforming early cancer diagnosis.
*Oncology
This study introduces a semi-automated platform for synthesizing fluorogenic probes to detect peptidase and protease activities at the single-molecule level. By applying this method to blood samples, researchers identified specific activity-based biomarkers for early-stage pancreatic tumors. The study's innovation lies in its use of single-molecule enzyme activity screening to detect altered enzyme activities in blood, offering a promising approach for early pancreatic tumor diagnosis.
*Oncology
This study conducts a proteogenomic analysis of glioblastoma evolution, revealing that highly proliferative states at diagnosis transition to neuronal states in recurrent tumors through activation of the WNT/PCP pathway and BRAF kinase. It also demonstrates that inhibiting BRAF kinase can impair this transition and improve the efficacy of treatments like temozolomide in patient-derived models, offering insights into potential therapeutic strategies for glioblastoma.
*Neurology
This study identifies five molecular subtypes of Alzheimer's disease (AD) using cerebrospinal fluid proteomics. Analyzing 1,058 proteins from 419 AD patients and 187 controls, the study reveals distinct protein level alterations associated with each subtype. These subtypes include neuronal hyperplasticity, innate immune activation, RNA dysregulation, choroid plexus dysfunction, and blood-brain barrier impairment. Each subtype is linked to specific genetic risk variants, showcasing a correlation with clinical outcomes and brain atrophy patterns. This discovery of molecular heterogeneity in AD underlines the necessity for personalized medicine in its treatment.
*Neurology
This study investigated the relationship between various inflammatory biomarkers in cerebrospinal fluid and changes in brain structure and cognition, particularly in Alzheimer's disease. It identified distinct inflammatory signatures, with one linked to preserved brain structure and cognitive function, suggesting a protective response, and another associated with diminished brain integrity and memory performance, indicating a detrimental impact. These findings highlight the complex role of inflammation in neurodegenerative diseases and suggest potential targets for therapeutic interventions.
*Infectious Disease
This study explores factors influencing the response to COVID-19 vaccination by analyzing plasma and urine proteomics along with gut microbiota. It discovers that activation of the LXR/FXR pathway in plasma is linked to the production of ACE2-RBD-inhibiting antibodies, and urine proteins are correlated with neutralizing antibody production. Additionally, it finds a relationship between gut microbiota, plasma and urine proteins, and vaccination response, leading to the development of a predictive model for vaccine efficacy.
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Industry Update
*Acquisition
Merck & Co. has announced its acquisition of Harpoon Therapeutics Inc. for approximately $680 million. This strategic move adds Harpoon's innovative T-cell engager, HPN328, and other candidates to Merck's oncology pipeline. HPN328, targeting DLL3, shows promise in treating small cell lung cancer and neuroendocrine tumors. The acquisition enhances Merck's capabilities in cancer immunotherapy, utilizing Harpoon's TriTAC? and ProTriTAC? platforms for developing treatments that engage the patient's immune system to target and destroy cancer cells. The deal is expected to close in the first half of 2024, subject to customary conditions and approvals.
*Acquisition
Johnson & Johnson (J&J) has announced a definitive agreement to acquire Ambrx Biopharma, Inc. for about $2.0 billion, enhancing its oncology portfolio. Ambrx's lead product, ARX517, targets prostate cancer, while other programs focus on breast and renal cell cancers. The acquisition strengthens J&J's capabilities in developing Antibody Drug Conjugates (ADCs) for precise cancer treatment. This strategic move aligns with J&J's commitment to innovating in oncology, leveraging Ambrx's technology for creating efficient ADCs with limited side effects. The merger, subject to approvals, should conclude in the first half of 2024, post which Ambrx will cease NASDAQ trading.
*Acquisition
GSK announced the acquisition of Aiolos Bio for $1 billion upfront, plus up to $400 million in regulatory milestones. This deal expands GSK's respiratory pipeline with Aiolos' phase II-ready, long-acting antibody AIO-001, targeting the TSLP pathway. AIO-001 offers potential treatment for asthma and other respiratory conditions, with the possibility of bi-annual dosing. Aiolos Bio, established in 2023, focuses on innovative respiratory disease treatments. The transaction is pending regulatory approvals.
*Acquisition
Novartis has announced its acquisition of Calypso Biotech, a former Merck Serono spinoff, for an upfront cost of $250 million. Calypso specializes in targeting the inflammatory cytokine interleukin-15 (IL-15) with its leading candidate, CALY-002. This drug, considered a "pipeline-in-a-drug," is currently in Phase 1b trials for celiac disease and eosinophilic esophagitis. Novartis aims to explore its broader potential across various autoimmune indications. Additionally, Calypso's shareholders stand to gain an extra $175 million if all developmental milestones are met. This acquisition is part of Novartis CEO Vas Narasimhan's strategy to focus on four key R&D pillars, following the company's restructuring and pipeline optimization last year.
*Partnership
Alphabet's Isomorphic Labs has entered into partnerships with Eli Lilly and Novartis, leveraging its AI technology for small molecule drug development. Developed from Google DeepMind's pioneering research, Isomorphic's AI platform aims to accelerate the drug discovery process. Under the agreements, Isomorphic will receive $45 million upfront from Lilly and $37.5 million from Novartis, with potential performance-based milestones reaching up to $1.7 billion and $1.2 billion, respectively, plus royalties.
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