Acuitas Therapeutics, Inc.’s Post

The chemotherapeutic drug CX-5461 is a potent mutagen in cultured human cells The chemotherapeutic agent CX-5461, or pidnarulex, has been fast-tracked by the United States Food and Drug Administration for early-stage clinical studies of BRCA1-, BRCA2- and PALB2-mutated cancers. It is under investigation in phase I and II trials. Here, we find that, although CX-5461 exhibits synthetic lethality in BRCA1-/BRCA2-deficient cells, it also causes extensive, nonselective, collateral mutagenesis in all three cell lines tested, to magnitudes that exceed known environmental carcinogens. https://lnkd.in/eJAT7ZMR

Wondering if combining LCMS with a benchtop NMR Spinsolve 80 MHz is enough to confirm the structure of new active pharmaceutical ingredients?  Absolutely! Check out the work by PMCisochem in their recent publication. They synthesized a vast library of compounds to screen Sirt3 modulators, and 1D 1H- and 13C NMR played a crucial role in confirming the structures. While the publication presents 1D results, it's worth noting that 2D techniques like COSY, HSQC-ME, and HMBC (readily available on the Spinsolves) are immensely helpful in this task. Just FYI, Sirt3 is a fascinating protein that regulates metabolism in mitochondria – crucial for many organs. It acts as a key player in mitochondrial metabolism and is mainly found in tissues rich in mitochondria. Sirt3 has become a promising therapeutic target for various diseases. #NMR #benchtopNMR #magritek #drugdiscovery #chemistry https://lnkd.in/eRXJ9Gxp

We at Helix are immensely proud when our work with clients and collaborators like Quellis Biosciences and Astria Therapeutics advances science and deepens our understanding of groundbreaking biology. Our recent collaboration involving the Cryo-EM structure determination of STAR-0215, PDB code 8FGX, showcases our commitment to pushing the boundaries of medical research. This pioneering work is part of developing a long-acting treatment for Hereditary Angioedema (HAE), aiming to drastically reduce the frequency of severe HAE attacks with less frequent dosing ( https://loom.ly/aFMlDn4 ). Being a part of such transformative projects with Quellis Biosciences and Astria Therapeutics not only fuels our passion for innovation but also underscores our role in driving significant advancements in healthcare. We are honored to contribute to this vital breakthrough and excited about the potential impacts on patient care worldwide. And get the article... it's accessible at no cost! Did you know… Our expertise in antibodies and Cryo-EM and X-ray services can help unlock your project's potential? Bring us your antibodies and let us deliver the structural insights you need to succeed! (Check us out here: https://loom.ly/6G84si4) #cryoem #crystallization #crystallography #drugdiscovery #drugdesign #protein #proteins #dna #rna #antibody #antibodies #science #nature #research #bio #bionetwork #biotechnology #biotech #bioscience #biotechnologyindustry #biopharma #drugdesign #drugdevelopment #pharmaceuticals #pharma #drug #lifesciences #lifescience

🔬Citation Break!📖 This citation investigates the relationship between Beta-Amyloid peptides and Amylin (IAPP). Through their research, the authors show a potential therapeutic target in the AMY3 receptor and the importance of developing compounds to help treat neurodegenerative conditions. Our Beta-Amyloid 1-42 (Cat# A-1002) and 42-1 were used in the drug treatment phase of the research. Paper: https://t.ly/vQwED Beta-Amyloid 1-42: https://t.ly/OrjdL #Research #Development #Experiment #BetaAmyloid #Peptide #rPeptide

Gene&Cell Therapy >> Poseida shares incremental Phase 1 update for Roche-partnered off-the-shelf CAR-T: Poseida Therapeutics said that 21 of 23 patients (91%) responded to the allogeneic CAR-T therapy it’s developing with Roche when given a higher dose of a chemo drug called cyclophosphamide than is typical. In addition, five of the 23 patients achieved a complete response, or stringent complete response, after receiving P-BCMA-ALLO1 and the higher chemo dose, the company said Friday. Separately, Poseida disclosed Friday in an SEC filing that Roche did not pick up an option for another CAR-T program targeting both BCMA and CD19. Poseida’s shares $PSTX ticked down in Monday morning trading, dipping about 3%. The updates follow Poseida’s presentation at the American Society of Hematology’s annual meeting last December. The company said then that data were “highly dependent” on patients’ cyclophosphamide regimens. Patients who took lower levels of cyclophosphamide before receiving P-BCMA-ALLO1 infusions did not respond to the CAR-T. Those results were recorded after just four weeks, raising questions about the durability of the therapy. The newest results come from a trial arm that Poseida said has an “optimized” level of cyclophosphamide at 750 mg/m2, allowing the chemo to clear out enough space in patients’ bone marrow for the CAR-T to have an effect. Median follow-up was 3.5 months, according to Poseida. Cyclophosphamide is typically given at 300 mg/m2, though it can be given in higher doses in conjunction with CAR-T. Increasing cyclophosphamide doses across trial arms appear correlated with “increased CAR-T cell expansion and persistence,” according to a note that William Blair analyst Sami Corwin wrote to investors on Friday. She added that the 91% overall response rate was higher compared to the pooled ORR of 54% from all cohorts. Corwin also suggested P-BCMA-ALLO1 could have a benefit regardless if patients previously received BCMA-targeting therapies, pointing out that all nine BCMA-naïve individuals achieved a response. There were also two patients in the 750 mg/m2 cohort who were retreated with the CAR-T at the discretion of their physicians. Poseida and Roche will move forward with the 750 mg/m2 cyclophosphamide regimen in a Phase 1b expansion study that is expected to begin “shortly,” Poseida execs said Saturday on an investor call. Poseida will receive an undisclosed milestone payment for launching the trial. ASH follow-up  On top of the new cohort data, Poseida also provided updates from earlier cohorts testing other levels of cyclophosphamide. In the lowest cyclophosphamide regimen of 300 mg/m2, five of 24 patients (21%) responded, though there were no complete responses. That’s up from zero out of eight responses as reported at ASH. (Patients in this cohort received varying doses of CAR-T.) In the… #lucidquest #genetherapy #celltherapy

Review (2021): Overcoming the challenges of tissue delivery for #oligonucleotide therapeutics #antisense oligonucleotides (#ASOs) #siRNA https://lnkd.in/eQbfRdne

Enhance precision and versatility in your Complement-Dependent Cytotoxicity (CDC) evaluation with our new bioassay. Our NEW CDC bioassay offers the possibility of expressing specific surface antigens to pinpoint the Mechanism of Action (MoA). This assay is instrumental in determining the MoA of Antibody mediated-CDC induction and therapeutics targeting the inhibition of CDC activity. https://hubs.ly/Q02dp7Xm0 #bispecificantibodies #bioassay #cellbasedassays #iLite #iLiteTechnology #CDC #ComplementBiology #ComplementingLifeScience #ComplementTherapeutics #Antibodies

Lipid Nanoparticle (LNP)- Mediated Delivery of BioPROTACs: BioPROTACs, also known as ubiquibodies, are recombinant protein-based degraders created by fusing a protein-based binder to an E3 ligase or E3 adapter. These biologics selectively ubiquitinate target proteins for ubiquitin-proteasome system (UPS)-mediated degradation, differing from small-molecule PROTACs by directly fusing warheads to E3 domains without relying on endogenous ligase recruitment. A recent study reported by researchers from the University of Pennsylvania utilized lipid nanoparticles (LNPs) for bioPROTAC encapsulation, achieving 95% GFP-KRAS elimination and doubling delivery efficiency over Lipofectamine. BioPROTACs effectively degraded endogenous Ras across multiple cell types. Their modular format allows for easy reprogramming to target various clinically relevant proteins. The study demonstrated rapid, specific intracellular protein degradation and significant antiproliferative effects of Ras-degrading bioPROTACs in pancreatic cancer cells, highlighting their potential as a therapeutic modality for undruggable or resistant proteins. Link to the article: https://lnkd.in/gnSY8B5c #bioprotac #ubiquibodies #AdPROM #protac #cancertherapy #lipidnanoparticles #lnp #nanoparticles #targetedproteindegradation Rebecca Haley David Gonzalez-Martinez Lukasz Bugaj George Burslem Michael J Mitchell & Andrew Tsourkas

Excited to have been part of the study on how HIV1-gp120 polymorphisms affect patients response to Fostemsavir 1 https://lnkd.in/e8F3pvDC In an early-stage drug discovery project for ViiV Healthcare, we at Domainex investigated the differential efficacy of Temsavir, an antiviral attachment inhibitor against the binding of HIV1-gp120 to human T-cell glycoprotein CD4.  Using the WaveRapid technology on Grating-coupled Interferometry (GCI), we helped Viiv correlate the binding association rates and sensitivities i.e faster association rates of gp120 binding to CD4 correlated with higher sensitivity of the gp120 polymorphs to Temsavir #Domainex #Antiviral #GCI #Biophysics #BindingKinetics

#BIO101s… The future of ultrarare diseases… #RARE, #DNLI, #RGNX… FDA #Biocentury #IONS… n-Lorem Foundation 🔮 Ultragenyx Pharmaceutical Inc. (#RARE), Denali Therapeutics Inc. (#DNLI) and RegenxBio Inc. (#RGNX) “agreed to share data on their unapproved therapies… 👏 They each have or will soon have data that could support a biomarker-based review of a neuronal MPS treatment.” A “consistent approach at CDER and CBER to endpoints and clinical trial designs for neuronal MPS disorders… could be a major step forward.” Add on top a better technology (like mass spectrometry) and maybe safe therapies for ultrarare diseases like MPS (mucopolysaccharidoses) will be approved sooner, rather than having patients wait for years, which will be too late for some… There are so many ultrarare disease patients in the world who deserve more options. Yesterday’s BioCentury Inc.’s article on the MPS biomarker workshop is promising, especially for gene therapies from firms above, however mRNA based therapies from Ionis Pharmaceuticals, Inc. (IONS) for example can also be great alternatives, especially when applied to ultra ultra rare patients, as experimented by the n-Lorem Foundation 🔮 GC Source: Steve Usdin / BioCentury Inc. (Great article Steve, hope to see you again soon! Drink in Miami on March 12-13?)