Speaking of Science’s Post

We are proud to announce the launch of new clinico-genomic datasets to enable life science companies to drive precision medicine drug discovery and development. Built through Helix’s extensive health system partnerships, these population-scale cohorts consist of full longitudinal clinical and genomic records that span multiple therapeutic areas including Cardiovascular, Immunology & Inflammation and Metabolic conditions. Helix CEO and co-founder James Lu, M.D. Ph.D: “As the number of precision therapies in development continues to rapidly expand, clinico-genomic data provide incredible opportunities to develop targeted therapeutics with better safety and efficacy profiles.” Hylton Kalvaria, Chief Commercial Officer of Helix: “Life science researchers can utilize Helix’s diverse clinico-genomic cohorts to better understand genetic factors associated with disease progression and clinical outcomes, as well as validating therapeutic candidates of interest.” #lifesciences #genomics #drugdiscovery #precisionmedicine You can read more about today’s announcement here: https://bwnews.pr/4b0Grip

Congratulations to all co-authors! This study shows why it is important to put patients first and follow their journey to try to understand fundamental questions for improving patient care. We profiled patients before and after treatment with the most commonly used advanced therapy for IBD, anti-tumour necrosis factor (anti-TNF). The beneficial effects of anti-TNF in autoimmune diseases were first discovered at the Kennedy Institute of Rheumatology in the 1990s and revolutionised patient care. However, this treatment does not work in four out of ten patients - and here we have leveraged high-resolution tissue profiling approaches to try to understand why. For a very quick overview also check out: https://lnkd.in/dqcM3bPK

Lack of high-quality cellular data rooted in clinical, and therapeutic context are mission-critical gaps in I&I research and drug discovery today. With a plethora of advanced therapy options now available to treat IBD, it is imperative to not just view the cellular landscape and associated drug discovery through the lens of "healthy Vs inflammation" but rather in context of "what is in the clinic today and what may enter it tomorrow". No model is better than human disease. Today, we present an in-vivo perturbation atlas of ~1M cells profiling biologic-naive patients with Crohn's disease and ulcerative colitis before and after treatment with the most widely used biologic agent in the world, adalimumab (an anti-TNF agent). This is the largest stand-alone scRNAseq atlas in IBD to date in the number of cells, and the first to profile anti-TNF therapy in both diseases longitudinally. Given anti-TNF is still the most common choice for initial biologic agent in clinic today globally, our hope is that this serves as a foundation for future perturbation atlases in IBD and autoimmunity globally. Many thanks to colleagues at the Kennedy, TGLU, Birmingham and Celsius Therapeutics for helping bring this vision to fruition. Christopher Buckley, Calliope Dendrou, Holm Uhlig Simon Travis, Matthias Friedrich, Mathilde Pohin, Devika Agarwal, Charlotte Rich-Griffin, Andrew Filer, Noah Spies, Piotr Bielecki, Ray Pagliarini, Tariq Kassum https://lnkd.in/gmwn8n7F

Thrilled to announce our partnership with Scipher Medicine! Together we will transform the autoimmune space by combining the powerful clinical data of OMNY Health's national network with the rich genomic insights from PrismRA, a personalized blood test for #rheumatoidarthritis. Looking forward to this seeing this novel precision medicine collaboration fueling the development of more targeted therapies and improving overall patient outcomes for #autoimmune patients.

Scipher Medicine and OMNY Health today announced a partnership to advance precision medicine efforts for immunology. This collaboration marks a significant leap forward in the fight against autoimmune diseases, integrating transcriptomic data from Scipher with OMNY Health's vast EHR network that reaches more than 80 million patients. OMNY Health’s network includes data from nearly 250,000 patients with rheumatoid arthritis (RA), which enables comprehensive tracking of patient outcomes and disease progression.   This partnership unlocks a wealth of information for researchers and drug developers. By combining the detailed clinical data within OMNY Health's network with the rich genomic insights from PrismRA, a personalized blood test for RA, researchers may gain a holistic view of the patient journey. This deeper understanding will fuel the development of more targeted therapies and improve overall patient outcomes.   #PrecisionMedicine #AutoimmuneDisease #RheumatoidArthritis #TargetedTherapy #RealWorldEvidence #ArtificialIntelligence https://lnkd.in/e825Xqp4

IL-40: A Promising Biomarker and Therapeutic Target for Sepsis ❗ Despite significant advances in clinical and scientific research, the mortality rate of sepsis remains high, largely due to the lack of precise biomarkers for patient stratification and therapeutic guidance. However, new research highlights Interleukin 40 (IL-40) as a novel cytokine that could change the prognosis and treatment strategies for sepsis. ⚡ Key findings from recent studies include: Elevated IL-40 in Sepsis: In two independent cohorts of septic patients, IL-40 levels were elevated at admission. High IL-40 levels were positively correlated with key markers of sepsis severity, such as PCT, CRP, lactate, and SOFA scores. This suggests IL-40 could be used to help identify critically ill patients at risk of early mortality. IL-40 and Sepsis Outcomes: In animal models, genetic knockout of IL-40 (IL-40−/−) improved outcomes in experimental sepsis, reducing cytokine storms, preventing multiple organ failure, and decreasing early mortality compared to wild-type mice. Mechanisms at Play: Single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) revealed that S100A8/9hi neutrophil influx and NET formation were central to IL-40’s role in exacerbating sepsis. Clinically, IL-40 levels in septic patients were correlated with the MPO/dsDNA ratio, a marker for neutrophil extracellular traps (NETs), suggesting a mechanistic link. IL-40 as a Therapeutic Target: Combining IL-40 knockout with antibiotic treatment (gentamycin) provided enhanced protection against polymicrobial sepsis compared to antibiotic treatment alone, demonstrating the potential of targeting IL-40 as a therapeutic strategy. In summary, IL-40 holds promise both as a novel prognostic biomarker and as a therapeutic target in sepsis, offering hope for improved patient stratification and more effective treatments. This research sets the stage for future clinical applications and highlights the need for further exploration into IL-40’s role in sepsis management. 🔗 https://lnkd.in/dACwhXKy #Sepsis #IL40 #Biomarkers #Cytokines #CriticalCare #MedicalResearch #TherapeuticTargets #Immunology #HealthInnovation

Scipher Medicine and Atropos Health announced a strategic partnership to accelerate precision medicine and expand the Immunology Multimodal Network, advancing shared decision-making for patients with rheumatoid arthritis. This collaboration will leverage Scipher's unique data and intelligence derived from its PrismRA precision medicine diagnostic and expand the Atropos Evidence™ Network, enhancing the immunology multimodal network on Atropos Health’s GENEVA OS™.   #PrecisionMedicine #AutoimmuneDisease #RheumatoidArthritis #RealWorldEvidence #ArtificialIntelligence   Link: https://lnkd.in/eESkfJTY

🎉 Congratulations to Andrea Villanueva-Raisman, Fredrik Edfors, and the entire team on their publication, "Advancing Chronic Liver Disease Diagnosis through Targeted Proteomics"! This collaborative study marks a significant stride in targeted proteomics and highlights ProteomEdge’s pivotal role in advancing both research and healthcare solutions. 🔗 Read the full article here: https://lnkd.in/dXyXxudn 💡 Our innovative approach allowed for the absolute quantification of 108 plasma proteins using just 2 microliters of blood, paving the way for a non-invasive method to detect and stratify liver fibrosis - a hallmark of chronic liver disease that often progresses silently to cirrhosis or cancer. 🩺 This work ultimately led to LiverEdge - our multiplex panel of 39 liver disease-related internal protein standards. With enhanced clinical compatibility, robust internal standards, and streamlined workflow, it offers a game-changing alternative to traditional liver biopsies, which are invasive and costly. 🔬 #liver #fibrosis #massspectrometry #precisionmedicine #ai #absolutequantification

American Association for the Study of Liver Diseases (AASLD) - A wrap 🙌 Last day of #AASLD, obviously with the ESSENCE phase 3 trial data for semaglutide being presented, and hitting both primary endpoints for MASH resolution (NAFLD Activity Score) and improvement in Fibrosis Stage. Big congrats to Novo Nordisk 🤩 Now, it is time for the preclinical MASH models to do their backtranslation for semaglutide treatment efficacy. Did we predict this? Furthermore, are the findings reproducibly? We have wrapped up our findings in our GAN DIO-MASH mouse model here: - Reproducible hepatoprotective effects and clinical translatability of semaglutide in the GAN diet-induced obese and biopsy-confirmed mouse model of MASH. Download: https://lnkd.in/d_BcH-m5 Our conclusion would be that improvement in NAFLD Activity Score for semaglutide is accomplished very consistently after 12-weeks of therapeutic intervention. This is supported by histological quantitative assessment for steatosis and inflammation. We also observe consistently across studies that plasma/liver biomarkers for fibrogenesis (HP, TIMP-1, PIIINP, a-SMA, ECM genes) are all moving in the right direction after 12-weeks of treatment. Albeit, longer treatment intervention (16+ weeks) would be needed for consistent histological improvement in fibrosis markers and especially Fibrosis Stage. I went back to #AASLD_2021 and found the below poster with 16-weeks of semaglutide treatment (sorry for the old layout 😌). Histological fibrosis markers (PSR, Col1a1) being reduced and delta fibrosis stage of 12% (ESSENCE demonstrated delta 15%). Note, statistical significance is a numbers game! Stay tuned for #EASL2025 where we will show the reproducibility and spot on clinical translatability for semaglutide after 24-weeks of treatment in GAN DIO-MASH mouse model! A little nerdy post (more sorry 😌) but at Gubra we pride ourselves to bring you conclusive translational data for you to make a go/no-go decision for your drug candidate. Semaglutide does seem to be the poster child for exploring clinical endpoints in a preclinical setting using the GAN DIO-MASH mouse!

Their abstract: Mitochondrial dysfunction is a hallmark of idiopathic neurodegenerative diseases, including Parkinson disease, amyotrophic lateral sclerosis, Alzheimer disease and Huntington disease. Familial forms of Parkinson disease and amyotrophic lateral sclerosis are often characterized by mutations in genes associated with mitophagy deficits. Therefore, enhancing the mitophagy pathway may represent a novel therapeutic approach to targeting an underlying pathogenic cause of neurodegenerative diseases, with the potential to deliver neuroprotection and disease modification, which is an important unmet need. Accumulating genetic, molecular and preclinical model-based evidence now supports targeting mitophagy in neurodegenerative diseases. Despite clinical development challenges, small-molecule-based approaches for selective mitophagy enhancement — namely, USP30 inhibitors and PINK1 activators — are entering phase I clinical trials for the first time.