Xilio Therapeutics, Inc.’s Post

Interested in Enhancing Antitumor Immunity? Dendritic cells are antigen-presenting cells that are essential for the initial activation of adaptive antitumor immunity. CD1D expression on DCs is required for presenting antigens to NKT cells and activating cytotoxic T cells.  Furthermore, CD1D+ DCs were concomitant with a higher expression of costimulatory molecules. Our humanized mouse models provide a robust preclinical platform for in vivo efficacy evaluation of novel therapeutics. Check out our humanized B-hCD1D mice (https://lnkd.in/e2xgJ_hK) and B-hCD80 mice (https://lnkd.in/duuFfBmq). #mousemodel #tumormodel #immunecheckpoint #humanizedmodel #preclinicalresearch #invivo #therapeutics #immunotherapy #antitumortherapy #cancertherapy #cancerresearch

The phase 1 expansion study of our tumor microenvironment modulator VT1021 has been published in Nature Communications Medicine. This paper focuses on safety, preliminary efficacy, and the exploratory biomarker study of VT1021 in patients with advanced solid tumors. Currently, VT1021 is under Phase 2/3 trial in GBM. Excited! #VT1021 #Immunotherapy #Oncology #Clinical #Phase1 #safety #efficacy #biomarker

I am happy to share our research publication, " Immobilized doxorubicin and ribociclib carbamate linkers encaged in surface modified cubosomes spatially target tumor reductive environment to enhance antitumor efficacy." This article has been published in #BiomaterialsAdvances (Impact Factor 7.9; Scopus Q1). Article link: https://lnkd.in/gdkHHyVk #PublicationAlert #PharmaceuticalSciences #PharmaceuticalResearch #BiomaterialsAdvances #Elsevier

Metastatic, refractory, and relapsed hepatoblastoma (HB) presents a significant therapeutic challenge, with patient survival rates below 50% due to lack of treatment options. As there have been proposals of histone deacetylase (HDAC) inhibition being used as a potential therapeutic strategy for HB, Andres F. Espinoza et al. developed a preclinical testing pipeline and investigated the effectiveness of panobinostat, an HDAC inhibitor, in combination with chemotherapy. They found that in comparison with normal livers, HB tumors exhibited higher levels of HDAC RNA and protein and showed that the combination therapy of panobinostat and VI chemotherapy constituted effective treatment for patients with high-risk, relapsed, and refractory HB. Their findings provided a rationale for further clinical investigation. https://lnkd.in/g2TZdicf

This article is a must-read for all ADC fans. Currently there are 11 FDA-approved ADCs for at least 20 indications including 4 new ADCs that were approved within the past 3 years. In this Review, Dr Tsuchikama et al. (The University of Texas Health Science Center) provide a brief overview of the basic molecular design of an ADC and how each ADC component (the antibody, linker, payload and conjugation chemistry) can affect the physicochemical and biophysical properties of the final product, including intracellular payload trafficking and metabolism, antitumor activity and safety profiles. The authors further provide an excellent overview of 5 classes of novel ADCs that are currently in preclinical and clinical development, including (1) bispecific ADCs, (2) probody-drug conjugates (PDCs), (3) immune-stimulating antibody conjugates (ISACs), (4) degrader-antibody conjugates (DACs) and (5) dual-drug ADCs.

July Featured Article: Novel therapeutics for small abdominal aortic aneurysms: Recommendations for rodent model research @honglu227 @curciAAA @BloodVesselDoc1 https://lnkd.in/gKbpZ93r

𝗙𝗗𝗔 𝗔𝗽𝗽𝗿𝗼𝘃𝗲𝘀 𝗘𝗮𝗿𝗹𝘆 𝗦𝘁𝗮𝗴𝗲 𝗖𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝗧𝗿𝗶𝗮𝗹𝘀 𝗳𝗼𝗿 𝗔𝗯𝗮𝘁𝗮 𝗧x' 𝗜𝗡𝗗 𝗳𝗼𝗿 𝗔𝗕𝗔-𝟭𝟬𝟭 𝘁𝗼 𝗯𝗲 𝘂𝘀𝗲𝗱 𝗶𝗻 𝗠𝘂𝗹𝘁𝗶𝗽𝗹𝗲 𝗦𝗰𝗹𝗲𝗿𝗼𝘀𝗶𝘀 New treatment Abata Therapeutics announces FDA clearance for the Phase 1 clinical trial of ABA-101, an autologous TCR-Treg cell therapy designed to treat progressive multiple sclerosis (MS) by targeting CNS-compartmentalised inflammation. #MultipleSclerosis #CellTherapy Preclinical success Preclinical studies show ABA-101 is safe and effective, demonstrating tissue-specific trafficking and robust suppression of inflammation. #ClinicalTrials #Inflammation How it works: ABA-101 is an autologous Treg therapy designed for MS patients with specific HLA markers. It engineers a patient's Tregs to recognise immunogenic myelin fragments in the CNS, offering targeted anti-inflammatory effects. Read more: https://lnkd.in/eXrp8HKg Image credits: https://lnkd.in/eBskHYG3

Kazia Therapeutics Limited is pleased to announced the early conclusion of an important two-part Phase I trial based on positive safety and promising clinical response findings observed to date. This investigator-initiated trial is evaluating the use of paxalisib with radiation therapy for the treatment of patients with PI3K pathway mutation brain metastases from solid tumors. Kazia's CEO, John Friend, shared his enthusiasm: “We are now preparing to engage with the Food and Drug Administration to discuss the data and seek guidance on the conduct of a pivotal registration study, with the goal of rapidly progressing paxalisib’s development to potentially provide a more effective treatment option for patients with brain metastases.” Learn more in our press release update here: https://shorturl.at/zAKX0 #paxalisib #brainmetastases #DMGs #DPIG

Medicus Pharma, led by Dr. Raza Bokhari, has submitted an updated Phase 2 clinical protocol to the FDA for a novel treatment targeting basal cell carcinoma. The protocol leverages micro-needle arrays containing doxorubicin, developed by Skinject, Inc., a subsidiary of Medicus Pharma. The submission incorporates enhancements to Chemistry, Manufacturing, and Controls (CMC), stability, and sterility data, addressing previous FDA comments. Notably, it introduces artificial intelligence and confocal microscopy as supplementary endpoints at one clinical site, promising deeper insights into treatment outcomes. 'This updated protocol is well-positioned to receive FDA approval, allowing us to commence participant randomization potentially before the end of this quarter,' stated Dr. Bokhari. The submission underscores Medicus Pharma's commitment to advancing innovative skin cancer treatments through rigorous clinical research and cutting-edge technology. @medicuspharma #skincancer #clinicaltrials #innovation

Drug discovery for molecular glues in the last few years has largely been driven by the desire to identify degraders for target proteins, and while this remains an active field, glues with non-degrading properties are receiving more attention. NST-628, developed by Nested Therapeutics (Cambridge, MA), is a non-degrading molecular glue that promotes the interaction of A,B and C-RAF to MEK1. These complexes are inactive, and prevent signalling through the Ras pathway, which blocks downstream activation of ERK. NST-628 has good PK properties, and is brain penetrant, which is an opportunity to address cancer cells hiding out in the brain, potentially offering a treatment option for either primary or metastatic brain tumours. As reported by Ryan et al., (paper link below), the compound is well tolerated in pre-clinical in vivo models and leads to robust reduction in tumour growth. In combination with Sotorasib, low dose NST-628 show dramatic reduction in tumour growth, indicating that combination therapy could be promising. A phase 1 clinical trial for safety, PK and preliminary efficacy in adult patients with MAPK pathway mutated/dependent advanced solid tumours is currently ongoing for this novel non-degrading molecular glue. Link to paper: https://lnkd.in/dyA96mi8 Clinical trial: https://lnkd.in/dhQSc5KZ #TPD #drugdiscovery #innovation #molecularglue Figure adapted from published report