Umoja Biopharma Announces Publication in Blood Highlighting Successful Generation of In Vivo CAR T-cells in Non-Human Primate Modeling First landmark, peer-reviewed publication of successful in vivo CAR T-cell data in an immune competent NHP model Data validate the VivoVec™ platform in a translationally relevant model and support its transition into human clinical testing, offering a potential paradigm shift in the field of CAR T-cell therapies Key Study Findings VivoVec particles (VVPs) incorporating CD80 and CD58 costimulation proteins exhibit enhanced capacity for in vivo CAR T-cell generation and produce CAR T-cells with increased antitumor functionality compared to those produced from VVPs displaying anti-CD3 scFvs alone. Combining the anti-CD3 scFv together with the ligand binding domains of CD80 and CD58 into a single multi-domain fusion (MDF) protein markedly augments the particles’ ability to bind, activate, and transduce T-cells. VVPs incorporating MDF compatible with NHP T-cell activation and costimulation potently generate anti-CD20 CAR T-cells in vivo, comprising up to 65% https://lnkd.in/eqsSTKjf
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Recent Clinical Updates From the Gene-Editing Field In this article, we look at recent clinical updates from the gene-editing field. These updates include clinical data from Vor Bio's ongoing Phase 1/2a trial of trem-cel in acute myeloid leukaemia, updated clinical data from Intellia Therapeutics' ongoing Phase 1 trial of NTLA-2001 in transthyretin amyloidosis, as well as IND clearance for Caribou Biosciences' acute myeloid leukaemia candidate, CB-012. Vor Bio presents positive data update on Trem-cell at ASTCT-EBMT 6th International Conference on Relapse After Transplant and Cellular Therapy Intellia shares new interim data from Phase 1 trial of NTLA-2001 in transthyretin amyloidosis Caribou Biosciences gets FDA green light to proceed with novel CAR-T candidate for AML https://lnkd.in/gXiMkGvP
News: Recent Clinical Updates From the Gene-Editing Field - CRISPR Medicine
crisprmedicinenews.com
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Immunotherapies for high grade.gliomas are currently in development and are mechanistically diverse, and each therapeutic approach involves complexities in preclinical and clinical study design that must be carefully considered for rigorous data to result. As more of these therapies are transitioned into clinical trials in pediatric and adult patients, a deep understanding of the expected local and systemic immunologic effects is essential to an appropriate trial design and incorporation of the appropriate bio-correlative studies. Successful clinical development of immunotherapies for HGG is likely to require a multi-institutional, consortia-based approach, with collaborations between academia and pharmaceutical companies. Here, the authors review in depth the TME in HGG, the various drivers of the anti-inflammatory TME in HGG, a current review of various immunotherapeutic approaches, and some of the recognized challenges to successful immunotherapy development. #highgradegliomatherapy #hggimmunotherapy
Development of immunotherapy for high-grade gliomas: Overcoming the immunosuppressive tumor microenvironment
ncbi.nlm.nih.gov
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Our groundbreaking paper just released!!! Exploring the anticancer properties of Azadirachta indica: In silico and in vitro study of its phytochemicals against hepatocellular carcinoma, Journal of Molecular Structure, Volume 1317, 2024, 138962, ISSN 0022-2860, https://lnkd.in/eJ2vrvt3. (https://lnkd.in/eGrM9JzU) by Hina Khalid, Sergey Shityakov, Carola Y. Förster, Yuanda Song, https://lnkd.in/eJ2vrvt3 https://lnkd.in/eJ2vrvt3 Abstract: The medicinal plant Azadirachta indica (Neem) interferes with carcinogenesis and acts as a tumor suppressor. This study evaluated the anticancer effects of a methanol extract of Azadirachta Indica on a human hepatocellular carcinoma cell line (HepG2) using an in vitro MTT assay. The results demonstrated that the methanol extract of Azadirachta Indica exhibited significant cytotoxicity against HepG2 cells, with an IC₅₀ value of 81.17 µg/ml. Furthermore, an in silico approach was used to investigate the interaction between Azadirachta indica and Akt1, a protein kinase implicated in the pathogenesis of hepatocellular carcinoma (HCC) via the PI3K/Akt/mTOR pathway. This study identified two promising Akt1 inhibitors, 2′,3′-dehydrosalannol and quercetin, with improved binding affinity (ΔGbind) and a safe pharmacological profile. These compounds also showed hepatoprotective effects. Molecular dynamics simulations, specifically the MM-GBSA model, were used to further scrutinize the inhibitory potential of the docked bioconstituents. The results suggest that the proposed in silico pipeline can be useful for identifying lead candidates for HCC through early-stage rational drug design. These candidates can then be verified in vitro and in vivo before being tested in clinical trials as mainstream targets against HCC. Keywords: Azadirachta indica; Neem; Hepatocellular carcinoma; Akt1 inhibitors; In silico drug design; Rational drug design
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"Those new and improved, cancer-killing (and cancer-identifying) machines are returned to the body, ready to start an all-out cellular war. Imagine your T-cells as mini-Terminators but without Arnold Schwarzenegger’s accent." #DahliaConsulting #BiopharmaceuticalIndustry #CommercialLifeSciences #ManagementConsultant #LifeSciencesBusinessStrategy #GlobalPharma #GlobalBioTech #SupplychainOperations #CommercialOperations #CGTcommercialization #Manufacturing #QualityAssurance #OperationalExcellence #FinancialAnalysis #OpModelDesign #LifeScience #BioTechnology #Bioprocessing #Biosimilars #BioPharmaIndustry #MedicalResearch #CDMO #GMP #GMPbatch #GMPmanufacturing #GenomeEditing #GeneTherapy #CellTherapy #Car_T #mRNA #cGMP #ClinicalGradeManufacturing #ClinicalGradeProduction #BiologicsLicenseApplication #BLA #Pharmaceuticals #RegenerativeMedicine #ChronicLymphocyticLeukemia #lymphoma #Leukemia #CancerKiller
Why CAR-T cell therapy is the cancer killer the world needs now
msn.com
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Excited to announce the release of our latest article published in Clinical Pharmacology and Therapeutics titled "Impact of Treatment Modality and Route of Administration on Cytokine Release Syndrome in Relapsed or Refractory Multiple Myeloma: A Meta-Analysis'. This analysis included data on CRS from 1,560 patients in 36 studies of BCMA-targeting CAR-Ts and bispecific antibodies (BsAbs). The analysis showed that BCMA CAR-T therapies exhibit higher CRS incidence, severity, longer CRS duration, and more prevalent tocilizumab usage compared to BsAbs. Further, SC administration of BsAbs was associated with lower incidence of CRS vs IV administration. Read the full article (available online): https://lnkd.in/g-cQP_a9 Thanks for all co-authors, specially Pooneh Soltantabar, PhD and Sheena Sharma, the two first authors who contributed equally to this work.
Impact of Treatment Modality and Route of Administration on Cytokine Release Syndrome in Relapsed or Refractory Multiple Myeloma: A Meta‐Analysis
ascpt.onlinelibrary.wiley.com
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"TRX103 is an investigational allogeneic off-the-shelf engineered T cell product generated from CD4+ cells sourced from healthy donors. These CD4+ cells are engineered to become cells that mimic the function of Tr1 regulatory T cells, called TRX cells. Tr1X is developing TRX103 for the treatment of several immune and inflammatory disorders. Multiple preclinical studies have shown TRX103 to be tolerable and effective and to have the potential to reset the immune system to a healthy state. TRX103 has the potential to overcome major limitations of current cell therapies for autoimmune diseases, which include limited persistence and side effects including cytokine release syndrome (CRS) and neurotoxicity." #DahliaConsulting #BiopharmaceuticalIndustry #CommercialLifeSciences #PMOStrategies #ManagementConsultant #LifeSciencesBusinessStrategy #GlobalPharma #GlobalBioTech #SupplychainOperations #CommercialOperations #CGTcommercialization #Manufacturing #QualityAssurance #OperationalExcellence #FinancialAnalysis #OpModelDesign #LifeScience #BioTechnology #Bioprocessing #StartupSuccess #CompliancewithPharma #OptimizingBusinessPerformance #Consulting #EfficientProjectDelivery #SuccessThroughPMO #PMO #ProjectManagementExcellence #PMOImplementation #Biosimilars #BioPharmaIndustry #BioPharmaceuticalConsulting #Pharmefex #Collaboration #PharmefexConsulting #MedicalResearch #CDMO #GMP #GMPbatch #GMPmanufacturing #GenomeEditing #GeneTherapy #CellTherapy #Car_T #mRNA #cGMP #ClinicalGradeManufacturing #ClinicalGradeProduction #BiologicsLicenseApplication #BLA #Pharma #Pharmaceuticals #RegenerativeMedicine #GlobeNewsWire #ClinicalTrials #Tr1XBio #GvHDTrial #FirstInClass #TRX103 #AutoImmuneSystem
Tr1X Announces First Patient Dosed in Proof of Concept GvHD Trial Evaluating TRX103, a First-in-Class Type 1 Treg (Tr1) Cell Therapy
globenewswire.com
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Sharing publication from my #pfizer colleague: "Impact of Treatment Modality and Route of Administration on Cytokine Release Syndrome in Relapsed or Refractory Multiple Myeloma: A Meta-Analysis", in Clinical Pharmacology and Therapeutics. Analyzed data on CRS from 1,560 patients in 36 studies of #BCMA-targeting CAR-Ts and bispecific antibodies (#BsAbs) for #multiplemyeloma
Excited to announce the release of our latest article published in Clinical Pharmacology and Therapeutics titled "Impact of Treatment Modality and Route of Administration on Cytokine Release Syndrome in Relapsed or Refractory Multiple Myeloma: A Meta-Analysis'. This analysis included data on CRS from 1,560 patients in 36 studies of BCMA-targeting CAR-Ts and bispecific antibodies (BsAbs). The analysis showed that BCMA CAR-T therapies exhibit higher CRS incidence, severity, longer CRS duration, and more prevalent tocilizumab usage compared to BsAbs. Further, SC administration of BsAbs was associated with lower incidence of CRS vs IV administration. Read the full article (available online): https://lnkd.in/g-cQP_a9 Thanks for all co-authors, specially Pooneh Soltantabar, PhD and Sheena Sharma, the two first authors who contributed equally to this work.
Impact of Treatment Modality and Route of Administration on Cytokine Release Syndrome in Relapsed or Refractory Multiple Myeloma: A Meta‐Analysis
ascpt.onlinelibrary.wiley.com
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Director, DMPK | AI augmented drug discovery | Experience in early discovery to Phase 1 | Curious | Generalist | Beginner's mind
Findings from this ASCPT survey- 92% of responses suggest that PD biomarkers are at least useful. Clinical Exposure-response modeling (57%) followed by pharmacokinetic (PK)/PD modeling (28%) are most preferred approaches for selecting doses. Dose optimization for antibody-drug conjugates was viewed to be moderately complex. The approved doses of 25 targeted therapies were examined and the average free concentration at steady state (Css) was determined to be similar to the in vitro cell potency (half-maximal inhibitory concentration (IC50) -the drug is an inhibitor of Porcupine, a membrane-bound O-acyltransferase required for Wnt secretion. Wnt pathway is expressed in skin tissues; AXIN2 mRNA expression in skin is a robust and sensitive biomarker for the Wnt pathway. A predominant safety issue in this case is dysgeusia. The authors performed integrated population PK and exposure-response analyses of PD biomarker and safety data to determine the recommended dose for expansion, rather than the conventional maximum tolerated approach.
Moving the needle for oncology dose optimization: A call for action
ascpt.onlinelibrary.wiley.com
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In a recently published paper, Zymeworks Inc. authors report details of the design and evaluation of ZD06519, a novel camptothecin payload for antibody-drug conjugates. From the abstract: Herein, we present the development of a novel camptothecin ZD06519 (FD1), which has been specifically designed for its application as an ADC payload. A panel of camptothecin analogs with different substituents at the C-7 and C-10 positions of the camptothecin core was prepared and tested in vitro. Selected compounds spanning a range of potency and hydrophilicity were elaborated into drug-linkers, conjugated to trastuzumab, and evaluated in vitro and in vivo. ZD06519 was selected on the basis of its favorable properties as a free molecule and as an antibody conjugate, which include moderate free payload potency (∼1 nmol/L), low hydrophobicity, strong bystander activity, robust plasma stability, and high-monomeric ADC content. When conjugated to different antibodies using a clinically validated MC-GGFG–based linker, ZD06519 demonstrated impressive efficacy in multiple cell line–derived xenograft models and noteworthy tolerability in healthy mice, rats, and non-human primates. #mabs #adcs https://lnkd.in/e42ya2Hq
Design and Evaluation of ZD06519, a Novel Camptothecin Payload for Antibody Drug Conjugates
aacrjournals.org
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Another exciting aspect of next-generation ADC innovation: novel payloads. The case in point in this article is the novel camptothecin payload, ZD06519 (FD1) developed by Zymeworks Inc. Thanks to Paul Moore and the folks at BioSpace for their opinion piece on how they see innovations like ZD06519 fitting into the wider next-gen ADC landscape. [ 𝑠𝑒𝑒 ℎ𝑡𝑡𝑝𝑠://𝑤𝑤𝑤.𝑏𝑖𝑜𝑠𝑝𝑎𝑐𝑒.𝑐𝑜𝑚/𝑎𝑟𝑡𝑖𝑐𝑙𝑒/𝑜𝑝𝑖𝑛𝑖𝑜𝑛-𝑡ℎ𝑒-𝑛𝑒𝑥𝑡-𝑔𝑒𝑛𝑒𝑟𝑎𝑡𝑖𝑜𝑛-𝑜𝑓-𝑎𝑑𝑐𝑠-𝑤𝑖𝑙𝑙-𝑖𝑚𝑝𝑟𝑜𝑣𝑒-𝑐𝑎𝑛𝑐𝑒𝑟-𝑡𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡/ ]
In a recently published paper, Zymeworks Inc. authors report details of the design and evaluation of ZD06519, a novel camptothecin payload for antibody-drug conjugates. From the abstract: Herein, we present the development of a novel camptothecin ZD06519 (FD1), which has been specifically designed for its application as an ADC payload. A panel of camptothecin analogs with different substituents at the C-7 and C-10 positions of the camptothecin core was prepared and tested in vitro. Selected compounds spanning a range of potency and hydrophilicity were elaborated into drug-linkers, conjugated to trastuzumab, and evaluated in vitro and in vivo. ZD06519 was selected on the basis of its favorable properties as a free molecule and as an antibody conjugate, which include moderate free payload potency (∼1 nmol/L), low hydrophobicity, strong bystander activity, robust plasma stability, and high-monomeric ADC content. When conjugated to different antibodies using a clinically validated MC-GGFG–based linker, ZD06519 demonstrated impressive efficacy in multiple cell line–derived xenograft models and noteworthy tolerability in healthy mice, rats, and non-human primates. #mabs #adcs https://lnkd.in/e42ya2Hq
Design and Evaluation of ZD06519, a Novel Camptothecin Payload for Antibody Drug Conjugates
aacrjournals.org
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