Erin Kimbrel

More insights into our understanding of molecular mechanisms regulating the differentiation and function of human Tfr cells.

20

Exciting advancement in cancer treatment. Alpha fetoprotein (AFP) has emerged as a next-generation Antibody Drug Conjugate (ADC), targeting cancer cells and myeloid-derived suppressor cells (MDSCs). What makes this approach promising is that AFP receptors (AFPRs) are found on most tumors and MDSCs while being absent on normal cells. By conjugating AFP with cytotoxic drugs, we can effectively target cancer cells and MDSCs with minimal off-target toxicity. This strategy not only tackles cancer cells directly but also enhances the lymphocyte-to-monocyte ratio (LMR). The accumulating evidence strongly supports the use of AFP conjugates in the fight against cancer. #CancerTreatment #immunooncology #MedicalAdvancements

42

1 Comment

It would be an informative conference for people developing oligonucleotide-based therapeutics; the Full agenda is now available. I will give a talk on our experiences with oligonucleotide mediated immune responses. Oligonucleotide Therapeutics Society

24

2 Comments

Lucky you, Fadi. With this lineup, I surely would have liked to be there! But for anyone in the Cambridge, MA area, this is a great chance to learn more about the use of #metabolomics and #multiomics in pharmaceutical research. Registration is free. Just follow the link in Fadi's post. #health #research #pharma

6

Personalized medicine for brain repair! I am pleased to share our report that cortical glia progenitor cells, specifically oligodendrocyte precursor cells, can be directly reprogrammed in vivo using a gene therapy approach to become neurons. This capacity demonstrates an additional therapeutic avenue to explore for replacing neurons lost to disease or injury. Targeting a patient’s own cells for neuronal replacement could avoid using costly, clinical-grade iPSC-derived cells, thus providing an additional lower-cost approach that may extend this therapeutic option for wider healthcare delivery. See the free, public-access full paper at: https://lnkd.in/gQdtHWx4 #brainrepair, #stemcells, #precisionmedicine, #regenerativemedicine, #reprogramming

32

1 Comment

On my next GEN live show, Stephen Sofen and Susan Abu-Absi join to discuss hot topics in #bioprocessing (the lifeblood of drug development). We will dive into trends in cell and gene therapy, automation, and how companies are scaling manufacturing to bring down the cost of goods. Also, how is the role of CDMOs evolving and what impact will AI have in transforming CGT manufacturing? Join us! Register 👇 https://lnkd.in/env9RuCY

11

Good to see further data from Inflection Biosciences Ltd showcasing the potential for dual PIM/PI3K inhibitor IBL-202 in peripheral T-cell lymphoma (PTCL), an indication with ongoing unmet medical need. Data shows IBL-202 to be more potent in pre-clinical models versus combination of PI3K therapy copanlisib with PIM inhibitor AZD1208. Well done to the team at Universitätsmedizin Göttingen.

28

Pfizer’s Paxlovid Ineffective Against Long COVID Using 15-Day Regimen: Study Here an abstract from study published in NEJM https://lnkd.in/eKUsrcNE Importance:  There is an urgent need to identify treatments for postacute sequelae of SARS-CoV-2 infection (PASC). Objective:  To assess the efficacy of a 15-day course of nirmatrelvir-ritonavir in reducing the severity of select PASC symptoms. Design, Setting, and Participants:  This was a 15-week blinded, placebo-controlled, randomized clinical trial conducted from November 2022 to September 2023 at Stanford University (California). The participants were adults with moderate to severe PASC symptoms of 3 months or longer duration. Interventions:  Participants were randomized 2:1 to treatment with oral nirmatrelvir-ritonavir (NMV/r, 300 mg and 100 mg) or with placebo-ritonavir (PBO/r) twice daily for 15 days. Main Outcomes and Measures:  Primary outcome was a pooled severity of 6 PASC symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms) based on a Likert scale score at 10 weeks. Secondary outcomes included symptom severity at different time points, symptom burden and relief, patient global measures, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, orthostatic vital signs, and sit-to-stand test change from baseline. Results:  Of the 155 participants (median [IQR] age, 43 [34-54] years; 92 [59%] females), 102 were randomized to the NMV/r group and 53 to the PBO/r group. Nearly all participants (n = 153) had received the primary series for COVID-19 vaccination. Mean (SD) time between index SARS-CoV-2 infection and randomization was 17.5 (9.1) months. There was no statistically significant difference in the model-derived severity outcome pooled across the 6 core symptoms at 10 weeks between the NMV/r and PBO/r groups. No statistically significant between-group differences were found at 10 weeks in the Patient Global Impression of Severity or Patient Global Impression of Change scores, summative symptom scores, and change from baseline to 10 weeks in PROMIS fatigue, dyspnea, cognitive function, and physical function measures. Adverse event rates were similar in NMV/r and PBO/r groups and mostly of low grade. Conclusions and Relevance:  The results of this randomized clinical trial showed that a 15-day course of NMV/r in a population of patients with PASC was generally safe but did not demonstrate a significant benefit for improving select PASC symptoms in a mostly vaccinated cohort with protracted symptom duration. Further studies are needed to determine the role of antivirals in the treatment of PASC.

2

2 Comments

Excellent service for your conjugation chemistry needs

5

Postdoc Position in Fibroblast Biology UT Southwestern Medical Center See the full job description on jobRxiv: https://lnkd.in/dpsxnQ6Y #cancer #cancer_biology #cancer_associated_fibroblast #fibroblast #postdoc #tumor_immunology #tumor_microenvironment

5

The rise and rise of bi-specifics   In this recent review article by Goebeler, Stuhler and Bargou https://lnkd.in/eMm8uui6, it's evident that bi-specifics are a growing field, with numerous formats …. and likely no single format will be ideal for all indications/mechanisms. Although the review is more geared towards the 11 currently approved and numerous bi-specifics in clinical trials, the potential to target more than two proteins in one molecule is proposed as an obvious next step for this area. With their natural biophysical advantages, VHH are an ideal solution for adding functionality to an existing molecule …. the review alludes to this at the end. Our own work in creating multi-specifics from our VHHs agrees. We'll continue to share our results in this area as we advance.   #bispecifics #VHH #halflifeextender #multispecifics #proteinengineering

21

1 Comment

CAR T cells have proven successful in clinical trials for blood cancers, and researchers are eager to apply the technology to other types of cancers and diseases. If your R&D strategy is leading you toward leveraging CAR T, you need this new white paper:

10

Allogeneic #celltherapies hold transformative potential in diseases with limited treatment options, helping repair, replace or rejuvenate damaged cells and tissues. If we are to deliver these therapies to all who could benefit, we must overcome key challenges in purity and scalability. I shared with Cell & Gene my insights on how Astellas Pharma is exploring non-integrating strategies and tools to enhance and expedite the creation of pluripotent stem cell-based therapies to potentially help treat more patients, faster. Read the full article here: https://bit.ly/3WRqrw7 #ScienceFirstForPatients #ChangingTomorrow

127

1 Comment

KANGAS PART 3 The complaint gives numerous examples of Illumina and GRAIL executives speaking of their close work with the FDA and Galleri's inevitable approval, and hence reimbursement. Then this: "[X] worked with both Defendants Aravanis and Ofman over his over-decade long career at Illumina and GRAIL and served as Associate Director of Key Accounts at GRAIL from 2020 through 2021. HE EXPLAINED THAT IT WAS COMMON KNOWLEDGE INSIDE THE COMPANY THAT THE FDA HAD INFORMED GRAIL THAT NONE OF THE CLINICAL DATA GENERATED FOR GALLERI WAS SUFFICIENT FOR FDA APPROVAL. " "As [X] explained, there was NO VIABLE PATHWAY to FDA approval because the FDA required clinical evidence that Galleri could in fact screen for 50 types of cancer, as Defendants publicly represented—but that this was an insurmountable task in light of the lack of any in-progress or proposed clinical trial or trials that would assess that outcome. As [X] reported, the FDA told GRAIL that its modeling data was not going to be sufficient; rather, GRAIL needed actual, clinical evidence that Galleri could in fact detect 50 cancers."

24

A grad student is turning spinach leaves into #heart tissue by mimicking vascular systems. This breakthrough in regenerative medicine could redefine transplants. What are your thoughts on this innovation? Worcester Polytechnic Institute

30

Well this is a big frickin' deal! The latest Advanced Research Projects Agency for Health (ARPA-H) program (funded throught the Biden Cancer Moonshot Program) is for an AT-HOME-MCED test 🤯🤯🤯 The program is being led by Ross Uhrich from Walter Reed Medical Center & the USUHS (fantastic institution by the way, I've worked with them). These programs are a big deal, particularly in VC Dx hard times - a recent ARPA-H program was funded for a total of $150M with individual grants of $20M-$30M. Great non-dilutive way to fund a newco! Article from Politico attached: "What the agency doesn’t want: another $1,000 cancer test that nobody uses." (poor GRAIL that's just plain mean 🤣) Here's the draft proposal (great read!): https://lnkd.in/gy_6w97t "POSEIDON aims to identify cancers at a stage when the tumors are more responsive and less costly to treat, thus saving lives and money for Americans. POSEIDON will develop sensors and synthetic reporters to be administered at home that can detect early-stage cancer with unmatched sensitivity and specificity. The synthetic reporters are shed in urine or breath and detected with a low-cost device that integrates telemedicine with user-friendly hardware and, if necessary, provides patients and clinicians a path forward follow-up diagnosis and care." "To accomplish this, POSEIDON builds upon two key disciplines: (1) Synthetic biology, which allows for engineering of cell-free and cell-based circuits with sophisticated sensing, signal analysis, and signal output functions, and (2) Multi-omic tumor profiling efforts, which combine genomics, transcriptomics, epigenomics, proteomics, volatilomics, and metabolomics to decipher features of tumor molecular landscapes." Critical IMO is the requirement for multiomics: reaching the sensitivity and specificity required by MCED clearly requires far higher performance than can come from a single omic 👏👏👏 In person Proposer's Day September 4th: https://lnkd.in/gwJffZh6 (lots of interesting information including "must have" and "optional" cancer targets) Teaming page: https://lnkd.in/g_6eZfBm Good chance for any smaller companies (e.g. an 'omics startup) to team up with a prime like Battelle to provide a sub-component for a few million. You can see who's already expressed interesting, including: Tufts University, Verily, Velsera, Battelle, University of Washington, University of Michigan, Boston Scientific, New York University, UCLA, Icahn School of Medicine at Mount Sinai (now that's ironic 🤣)

210

11 Comments

The attached review article of the emerging field of senolytic drug development (targeting senescent cells) is a great introductory read.

35