J&J Medical Affairs Oncology’s Post

In patients with various forms of transthyretin amyloidosis, including transthyretin amyloid polyneuropathy, a reliable, useful tool for investigating the disease and how to rank drug candidates is X-ray crystallography, according to findings from an analysis published in the journal Molecules MDPI. Read more: https://brnw.ch/21wHO69 #RareDisease

https://lnkd.in/eVVGJPEb h1218, a novel anti-CD19 scFv, differs from the current benchmark FMC63 in faster on- and off- rates, a lower effector-target avidity, and recognition of a membrane-proximal epitope on CD19. h1218 CAR-T cells showed reduced AICD and superior persistence in pre-clinical experiments. In a phase 1 study with 12 r/r B NHL patients treated, h1218 CAR-T produced promising durable potency, manageable toxicity, and altered serum cytokine profiles in patents. This report is a successful example for bench-to-bedside CAR-T development that reveals new mechanistic and clinical insights.

The ASC4FIRST trial was presented at ASCO, comparing asciminib to first and second generation TKIs in newly diagnosed CML.  Asciminib demonstrated superior MMR rates and side effect profiles compared to first and second generation TKIs.  In a subgroup analysis, this difference was statistically significant when compared to imatinib, and was not statistically significant when compared to the second generation TKIs, although asciminib was still numerically better.  What's more important to note, however, is that other outcomes like progression-free survival and overall survival have not read out yet.  Examining the side effect data, we can probably say that asciminib is better tolerated than the BCR-ABL TKIs.  Every TKI has its "signature" side effect, like edema or arterial occlusive events, which clinicians have to learn to manage.  In this trial, asciminib had 38% grade 3 or higher adverse events, compared to 44% for imatinib and 55% for the other TKIs.  From a clinical outcome perspective, it's not time to move to asciminib, but it may be a reasonable first line option for certain patients from a side effect standpoint. #scemblix #cml https://lnkd.in/eq3QNtRc https://lnkd.in/ekqxfjGM

To monitor the longer-term effects of MDM2 inhibition/p53 upregulation on engrafted chronic phase CML LSC in a scenario where therapy is removed (mimicking TKI discontinuation), we performed serial analysis of human cells at the end of a 28-day cycle of NIL + /- IDASA treatment, and then again after a 28-day treatment-free period (cohort 3, Fig.  4a )

In assigning magnitudes of clinical benefit, the ESMO guidelines consider the OS contributions of the experimental drug and HR values. For cancers with a survival expectancy of less than 12 months, the magnitude of clinical benefit of the experimental drug is highest if both the survival contribution is ≥3 months and the lowest HR boundary is ≤0.65 or its 2-year absolute survival contribution is ≥10%

Substantial clinical evidence links CSF heparan sulfate to clinical outcomes in neuronopathic #MPS patients and the FDA recently accepted the biomarker to support #AcceleratedApproval. A workshop hosted by the Reagan-Udall Foundation for the FDA earlier this year brought together industry, researchers, and advocates to discuss this evidence - and the speakers have now published a summary of their perspective on the path forward for neuronopathic MPS disorders. Learn more: https://lnkd.in/dNA49ThV #RareDisease

The goal of the KARDIA-2 trial was to evaluate zilebesiran compared with placebo among patients with uncontrolled hypertension. Zilebesiran is a subcutaneously injected RNA interference agent that targets hepatic synthesis of angiotensinogen (AGT), which is the most upstream precursor of all angiotensin peptides. Read the details of the clinical trial here: https://bit.ly/3xsVDqN #ACC24 #cvPrev

🔬 After +4 years of dedication, I am thrilled to announce that our latest research paper is now available online! 📚 In this research, we present a proof-of-concept approach to address the high allelic heterogeneity in ABCA4, which is a great challenge in designing therapies for STGD1. This strategy is based on delivering several antisense oligonucleotides embedded in U7snRNAs, providing the opportunity to target various splicing defects using a single therapeutic vector. 🔎 Read more about this study here: https://lnkd.in/dPKZDdBX 💡 The multiple antisense oligonucleotide delivery approach showed potential to rescue several splicing defects, and offers the possibility to target a larger group of STGD1 patients. However, the journey does not end here – more research is crucial to overcome the encountered challenges. 🙏 Big thanks to everyone involved in this research and those who supported me along the way. Your hard work made this possible, and I am really proud of what we have achieved together. Iris Riswick, Irene Vázquez Domínguez, Lonneke Duijkers, Dyah Karjosukarso, Davide Piccolo, Miriam Bauwens, Elfride De Baere, Michael Cheetham, Alejandro (Alex) Garanto and Rob Collin, many thanks. #StargardtDisease #ABCA4 #U7snRNA #AON #ASO

🆕 Foundation for the Accreditation of Cellular Therapy (FACT) and Joint Accreditation Committee ISCT-Europe & The EBMT (JACIE) have published a preliminary draft of both: ☑️ FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration, Ninth Edition (HCT 9 Standards), and ☑️ FACT-JACIE International Standards for Immune Effector Cells, Third Edition (IEC) 💡 Read the news article and discover more details 🔗 https://lnkd.in/dduDrkmf The drafts are now open for public comments which will be accepted until 15 December 2024. 📅 As the field of #CellularTherapy is continuously evolving, the goal for each new edition of the Standards is to accurately capture and reflect those changes to remain a relevant and useful resource for programs. The comments, suggestions, and feedback solicited during the public comment period are not only welcome, but vital to ensuring that we achieve this goal. 🔬 ✔️

PepGen has shared positive clinical data from the first dose cohort (5 mg/kg) of PGN-EDO51, the company’s lead investigational candidate for patients with #Duchenne whose mutations are amenable to exon 51-skipping. Learn more and watch the recording of the "Research Row: Strategies to Restore Dystrophin" session from PPMD's 30th Annual Conference here: https://lnkd.in/dPges6Ng