Lexeo Therapeutics’ Post

Hemophilia, a genetic disorder primarily affecting males, is characterized by deficiencies in clotting factors VIII (Hemophilia A) or IX (Hemophilia B). This deficiency impairs the blood's ability to clot and effectively seal wounds. Recent advances in treatment, including gene therapy, long-acting clotting factor replacements, and small molecule drugs, are revolutionizing care for hemophilia patients. Gene therapy shows exceptional promise by using viral vectors to introduce normal clotting factor genes into patients, potentially providing long-lasting therapeutic effects. Further research is targeting additional regulatory factors in the coagulation pathway, aiming to further enhance treatment outcomes. To aid in these advancements, we have carefully curated a list of over 20 essential targets and related reagents specifically for hemophilia research. https://bit.ly/3Q5Es4Z

Immune recognition of therapeutic cells is a significant barrier for developing cell therapies. While B2M and CIITA, which regulate HLA -I and HLA-II expression, respectively, are key players in the immune response, additional factors are involved. A new animal study from the University of Arizona (https://hubs.ly/Q02qMLYD0) identifies factors that regulate NK cells, phagocytosis, and complement that may be significant for the immune response to hESCs, in addition to B2M and CIITA. These factors represent new targets for gene editing of cell therapies to reduce immune rejections. Find out how REPROCELL can help with your gene editing program: https://hubs.ly/Q02qMV6q0

#Commentary now available! Comparative analysis of #nucleicacid delivery systems for #genetherapy: assessing viral and non-viral approaches with emphasis on #extracellularvesicles The potential of #nucleicacidtherapeutics lies in their ability to address genetic disorders by directly targeting and manipulating the underlying genetic material. However, the translation of nucleic acid therapeutic concepts into effective clinical interventions faces challenges. This Commentary #article navigates the complexities associated with nucleic acid therapeutics, with a particular focus on gene therapy, and explores the recent emergence of extracellular vesicles as a potential solution to overcome the hurdles in nucleic acid delivery. Access below:

Avista Therapeutics is advancing gene therapy by creating cell type-specific AAV vectors for targeted treatment of retinal disease. With a crossover of expertise in viral vector design and deep foundations in the clinical development space, our therapies have a clear path to the patient. Our goal is to treat rare, inherited retinal disease with a specific focus on restoring vision loss. Ultimately, what makes us stand out? High-throughput, empirical approach with built-in quantitative in vivo validation which allows for rapid translation of new gene therapies to the clinic. Learn more: avistatx.com

Casgevy and Lyfgenia: Two Gene Therapies for Sickle Cell Disease https://bit.ly/3RRjirn In two small trials, about 90% of patients who received myeloablative conditioning therapy followed by a single IV infusion of either exagamglogene autotemcel (Casgevy) or lovotibeglogene autotemcel (Lyfgenia), gene therapies prepared from autologous CD34+ hematopoietic stem cells, achieved marked reductions in the rates of vaso-occlusive events. The durability of the response beyond 1-2 years is unknown. Whether these very expensive gene therapies prevent the multiorgan dysfunction or neurologic complications of sickle cell disease remains to be established.

"Rationale for using centralized transduction inhibition assays in three phase 3 rAAV gene therapy clinical trials’’ was published in Molecular Therapy Methods & Clinical Development Assessing anti-AAV antibodies is an important consideration prior to Gene Therapy administration. This paper explores and discusses the clinical rationale for using centralized TI assays in Pfizer’s three phase 3 rAAV gene therapy clinical trials. https://lnkd.in/eUBNsYdv #rAAV #GeneTherapy

BridgeBio partners with biomanufacturer Resilience to produce early-stage AAV gene therapies https://lnkd.in/gxjAj_8x BridgeBio has tapped biomanufacturing company National Resilience to produce two of its early-phase adeno-associated virus (AAV) gene therapies in a partnership designed to run beyond clinical trials. Resilience is tasked to manufacture AAV5 gene therapy [...]

Here's another preliminary expt. showing our EDM gene delivery platform is not compromised to the presence of neutralizing antibodies frequently encountered in gene therapy - In vitro HT29 killing study with T-Vec + anti-PD-1 antibody in the presence of neutralizing antibodies (ENHEnS is our optimized EDM platform for viral delivery). Stay tuned:)

Presentation of the first clinical results for GNT0004 gene therapy for Duchenne Muscular Dystrophy: These results obtained with our drug candidate GNT0004 for Duchenne Muscular Dystrophy are very encouraging, particularly in patients treated at the highest dose, both in terms of microdystrophin expression and functional improvement. They enable us to prepare for the pivotal phase of the trial, and demonstrate how this innovative technology can provide solutions to one of the most complex genetic diseases. I would like to pay tribute to the expertise of our researchers and experts who have made these initial results possible.

Sickle Cell Gene Therapy 'Truly Transformative SAN DIEGO — A newly approved gene therapy product for sickle cell disease, lovotibeglogene autotemcel (lovo-cel, marketed as Lyfgenia), led to durable disease remissions for up to 5 years and almost complete elimination of dangerous and debilitating vaso-occlusive events, according to results of a long-term follow-up study. More specifically, a single infusion of lovo-cel led to complete resolution of vaso-occlusive events in 88% of patients, with 94% achieving complete resolution of severe events. All 10 adolescents in the study achieved complete resolution of vaso-occlusive events. Most patients remained free of vaso-occlusive events at their last follow-up.