Arctic Bioscience’s Post

Antisense oligonucleotides have made significant progress since their emergence, now recognized as a clinically approved modality for numerous severe and debilitating diseases. Professor Sudhir Agrawal D.Phil, FRSC, HAYA’s scientific advisor, has played a pivotal role in advancing the field of antisense oligonucleotides - chemistry, design, synthesis, and safety. As a key member of the HAYA team, Professor Agrawal's expertise and guidance have been instrumental to our mission of bringing breakthrough disease-modifying therapeutics with the potential for greater efficacy, safety, and accessibility to patients. For further insights into the development journey of antisense oligonucleotides: 👉 Considerations for Creating the Next Generation of RNA Therapeutics: Oligonucleotide Chemistry and Innate Immune Responses to Nucleic Acids 👉 Nucleic Acid Therapeutics: Successes, Milestones, and Upcoming Innovation https://lnkd.in/eA-y4uXD #antisense #RNAtherapeutics

Fresh off the press, first paper from PhD student, Jono Caukwell in JCIS. In this study we investigated behaviour of lipid nanoparticles after exposure to representative bacterial strains found in the gastrointestinal tract and skin. SAXS and PLM revealed that monoolein cubic and inverse hexagonal phases transformed into inverse hexagonal and inverse micellar cubic phases upon exposure to live Staphylococcus aureus. Enzymatic hydrolysis and cell membrane lipid transfer contribute to this effect, which significantly reduces drug release rates. These findings highlight how the human microbiome can impact lipidic nanomaterials’ structure and drug release properties, with strain-specific variations across patients and body regions. Thanks to co-authors: Livia Salvati Manni Karl Hassan Andrew Clulow Brett Neilan Salvatore Assenza https://lnkd.in/dsqKTekA

Recent study published in Nature Communications on the structural basis of CCR6 modulation by allosteric antagonists. The research reveals detailed insights into how small molecule antagonists, like OXM1 and OXM2, interact with CCR6 to disrupt its activation, offering new perspectives on targeting this receptor for chronic inflammatory diseases. The findings highlight the versatility of GPCR antagonism, providing valuable knowledge that could advance drug discovery efforts focused on CCR6. Exciting developments in the field of structural biology and drug design! #StructuralBiology #DrugDiscovery #GPCR #InflammationResearch https://lnkd.in/g5Xaqj3R

Gain Therapeutics' GT-02287 Aids in the Correct Folding of Glucocerebrosidase (GCase) and Prevents ER Retention, ER Stress, and ER-associated Degradation of Mutated GCase Enzyme. This week at AD/PD - Advances in Science & Therapy 2024, we presented data that addresses the mechanism of action of our lead clinical candidate GT-02287. As a result of its mechanism of action, GT-02287 treatment leads to a dose-response enhancement of GCase activity. The outcome was enhanced lysosomal activity and efficient processing of the GCase substrate glucosylceramide. Increase in GCase substrate in the lysosome was previously shown to be associated with accumulation of aggregated alpha-synuclein, a pathological hallmark of Parkinson’s disease and related disorders. “These data further confirm our understanding of the mechanism of action of GT-02287, how it impacts cellular health by preventing the downstream consequences of GCase misfolding, including cellular stress and lysosomal dysfunction” commented Natàlia Pérez Carmona, Senior Director of Biology at Gain Therapeutics and presenting author. #parkinsonsdisease #drugdiscovery #ai #drugdevelopment #biotechnology #cns #computationalbiology The full poster can be found on our website here: https://lnkd.in/g54AkdKS

Delighted to declare the reception of the National Science Foundation (NSF) ACCESS award for my research proposal concerning the Benchmarking Dynamics for Antibody Design. Gratitude is extended to my Principal Investigator, Professor Ryan Lee Hayes, whose unwavering support has been integral to the progression of this undertaking. The focal objective of this inquiry is the execution of a rigorous benchmarking investigation to assess the precision of λ dynamics in prognosticating the binding free energy associated with antibodies. Within the realm of alchemical methodologies, λ dynamics stands out for its distinctive scalability to the expansive sequence spaces inherent in protein design, thereby presenting an unparalleled and noteworthy capacity for therapeutic design. #antibodies #therapeutics #computationalbiology

I am pleased to share insights from our recent review article, which explores the advancements in Proteolysis Targeting Chimeras (PROTACs)—a revolutionary approach in Target Protein Degradation (TPD). In an era where numerous disease-causing proteins remain undruggable due to structural intricacies, PROTACs are demonstrating remarkable promise as a transformative tool in drug discovery. 🔬 What Are PROTACs? PROTACs are small, multifunctional molecules designed to facilitate the degradation of harmful proteins rather than merely inhibiting their activity. These unique molecules function by recruiting the protein of interest (POI) and an E3 ligase, thereby initiating the poly-ubiquitination process and effectively marking the POI for degradation via the ubiquitin-proteasome system (UPS). 🌐 Our Key Focus: Designing Optimal Ternary Complexes Through the application of advanced in-silico and biochemical methodologies, we investigated strategies for optimizing ternary complexes, a pivotal factor in the successful functioning of PROTACs. Our review underscores the significance of ligand selection, linker design, and computational approaches, all of which are essential for the formation of stable and cooperative ternary complexes. 💡 Why This Matters The therapeutic potential of PROTACs is substantial, with over 20 candidates currently undergoing clinical trials for conditions spanning from cancers to autoimmune diseases. This research endeavours to address the challenges associated with the stability, selectivity, and efficiency of PROTACs, thereby advancing our ability to develop effective treatments for previously untreatable diseases. Many thanks to Shareef Shaik and Professor Aravinda Pai for giving me this opportunity to be part of this informative review. 📘 Learn More For those seeking a comprehensive understanding of the scientific underpinnings, our article delves into intricate mechanisms, cutting-edge methodologies, and the pivotal role of linkers in stabilizing the ternary complex. By optimizing these factors, we aspire to accelerate the discovery of more efficacious PROTAC therapies. #DrugDiscovery #ProteinDegradation #PROTACs #TargetedTherapies

Currently, research in #obesity and weight loss is flourishing. At the European Congress on Obesity (#ECO) held in Venice, Italy from May 12th to 15th, a new study led by Professor Donna Ryan from the Pennington Biomedical Research Center was published in #NatureMedicine. This study found that #Semaglutide not only significantly reduces body weight, but its weight loss effects can last for four years and it can also reduce cardiovascular problems. In February of this year, the biotechnology company #BioAge, in collaboration with #EliLilly, initiated a Phase 2 clinical trial aimed at evaluating the efficacy of its investigational EP4 receptor agonist, Azelaprag, in combination with Eli Lilly's #Tirzepatide, for the treatment of obesity. Related products can be found in TargetMol T14390 Azelaprag https://lnkd.in/e-yvwYpS TP1111 Tirzepatide https://lnkd.in/eCXCuuKu T76860 Bimagrumab https://lnkd.in/e6RTEFXk #TargetMol #Obesity #inhibitors #innovation #diabetes

Insilico Medicine announced that following the initiation of Phase 1 clinical trials in Australia in November 2023, the company has achieved a key milestone by completing dosing for the first participant in Phase 1 clinical trials for its candidate, ISM5411, in China. ISM5411 is an oral, PHD 1/2-specific inhibitor that facilitates the treatment of IBD by inducing the expression of gut barrier protective genes. Dr. Feng Ren, Co-CEO and CSO of Insilico Medicine, said, "ISM5411 marks another candidate to advance into clinical trials both domestically and internationally, following our IPF project. With its unique mechanism targeting intestinal mucosal repair, ISM5411 demonstrates considerable innovation potential. Preclinical studies have shown its potential to reduce systemic side effects. Additionally, ISM5411 boasts favorable safety profiles and significant efficacy against colitis. We are enthusiastic about the prospect of advancing ISM5411, discovered through the synergy of artificial and human intelligence, to address the growing incidence of IBD." #BiotechInnovation #InflammatoryBowelDisease #QimingPortfolio #QimingHealthcare

Aliri is proud to be sharing an exciting lineup of highly relevant scientific presentations at the upcoming European Bioanalysis Forum Open Symposium, in Barcelona, Spain, this 20-22 November. Which of our #EBF presentations will you be stopping by? 👉 Featured Talk by David Bonnel, PhD: Integrating #MassSpectrometry Imaging and #SpatialTranscriptomics for Clinical Insights into Disease Complexity and Drug Response | 22 November from 14:40 – 15:00. 👉Poster: Quantifying and mapping #ATP distribution within tissues to inform targeted therapeutic strategies in drug development 👉Poster: Exploring the Spatial Distribution of #mRNA-Lipid Nanoparticles in Mouse Whole-Body and Isolated Organs Using #MALDI MSI 👉Poster: Maximizing Reproducibility and Sensitivity in #qPCR for Detecting Transcripts Over a Broad Dynamic Range in Response to Anti-PD-1 Therapy 👉Poster: Distribution of standard-of-care antituberculosis drugs in cynomolgus macaque lungs Request a meeting with our team at EBF! https://lnkd.in/e_ZxyS5S

Clene Nanomedicine, Inc. announces new biomarker and clinical efficacy data submitted to FDA in support of #CNMAu8 as a treatment for #ALS. New data from the HEALEY ALS Platform Trial demonstrate that participants treated with CNM-Au8 that have significant decreases in neurofilament light (NfL) not only show improved clinical survival and slowed functional decline, but also demonstrate increased biomarker signatures of improved mitochondrial energy metabolism and decreased measures of oxidative stress. Read the release here: https://bit.ly/3AmDSdT #ALSresearch #EndALS