Cusabio Technology LLC’s Post

#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:

Gene&Cell Therapy >> Pfizer’s Duchenne muscular dystrophy gene therapy fails Phase 3 trial: Pfizer’s Duchenne muscular dystrophy gene therapy failed to meet the primary and key secondary endpoints in a Phase 3 study, pointing to a bleak future for the program. The gene therapy failed to significantly improve motor function at one year in boys with Duchenne, measured using a 17-item scale that evaluates various aspects of mobility called the North Star Ambulatory Assessment. The therapy also did not significantly improve secondary endpoints such as 10-meter run/walk velocity and time-to-rise-from-floor velocity compared to placebo. “Pfizer will continue to closely monitor all participants enrolled in the study and is evaluating appropriate next steps for the program,” the company said Wednesday in a statement. Known as CIFFREO, the study enrolled 99 boys aged 4 through 7 with Duchenne muscular dystrophy, according to the federal clinical trials database. The participants received Pfizer’s fordadistrogene movaparvovec or placebo. There have been two patient deaths in Pfizer’s Duchenne gene therapy clinical studies. In May, Pfizer disclosed that a boy enrolled in a Phase 2 study for the therapy passed away, and it was investigating the patient’s death. As a result, the company paused the administration of the gene therapy to boys who had originally been in the placebo arm of the Phase 3 study. In 2021, Pfizer disclosed a boy in a Phase 1b study of the gene therapy died and later said he “had more advanced disease with underlying cardiac dysfunction.” The FDA granted accelerated approval last June to Sarepta Therapeutics’ Duchenne muscular dystrophy gene therapy for boys aged 4 to 5. Within the narrow group of patients eligible for Elevidys, demand has been high. The FDA is expected to decide by June 21 on whether to expand the eligible population based on mixed results from a confirmatory study. Last year, Pfizer took a step back from developing early-stage gene therapies, selling a suite of preclinical programs to AstraZeneca. #lucidquest #genetherapy #celltherapy

A new study published in Nature Magazine explores the potential of adeno-associated virus (AAV)-based gene therapy to help patients with Duchenne muscular dystrophy (DMD). The phase 3 EMBARK trial evaluated delandistrogene moxeparvovec, an AAV-rh74 gene therapy aimed at restoring dystrophin function. Although the primary endpoint showed no significant difference compared to placebo, secondary outcomes suggested some functional benefits, and the safety profile remained consistent with earlier studies. This research underscores the ongoing efforts to leverage AAV to address rare genetic conditions and improve patient outcomes. Read the full article here: https://lnkd.in/gUUnhk98

Single-cell omics and CRISPR technologies are two topics that are given plenty of attention in the current market, but haematology as a whole doesn't get quite the same level of consideration. The latest review on erythropoiesis gives an interesting overview on where we stand in the mechanisms of red blood cell formation. Aside from looking into findings around transcription factors and epigenetic modifications relating to erythropoiesis, the review highlights how this knowledge could result in novel approaches to rare diseases like Diamond-Blackfan anemia. Gene therapy for β-thalassemia is highlighted as one example of a potential way forwards, but as of February 2024 there are only 38 FDA approved CGT products on the market. This review gives me hope that innovations in single-cell omics and CRISPR technologies could mean more CGT products getting approval and seeing more haematology-focused businesses in the world. Do you see CGT as the future of biotech too? Are there any other therapeutic areas you'd want to see more focus on? Let's connect to talk about all things Omic!

LucidQuest Strategic Insights (lqventures.com) >>> Gene&Cell Therapy >> Pfizer’s Duchenne muscular dystrophy gene therapy fails Phase 3 trial: Pfizer’s Duchenne muscular dystrophy gene therapy failed to meet the primary and key secondary endpoints in a Phase 3 study, pointing to a bleak future for the program. The gene therapy failed to significantly improve motor function at one year in boys with Duchenne, measured using a 17-item scale that evaluates various aspects of mobility called the North Star Ambulatory Assessment. The therapy also did not significantly improve secondary endpoints such as 10-meter run/walk velocity and time-to-rise-from-floor velocity compared to placebo. “Pfizer will continue to closely monitor all participants enrolled in the study and is evaluating appropriate next steps for the program,” the company said Wednesday in a statement. Known as CIFFREO, the study enrolled 99 boys aged 4 through 7 with Duchenne muscular dystrophy, according to the federal clinical trials database. The participants received Pfizer’s fordadistrogene movaparvovec or placebo. There have been two patient deaths in Pfizer’s Duchenne gene therapy clinical studies. In May, Pfizer disclosed that a boy enrolled in a Phase 2 study for the therapy passed away, and it was investigating the patient’s death. As a result, the company paused the administration of the gene therapy to boys who had originally been in the placebo arm of the Phase 3 study. In 2021, Pfizer disclosed a boy in a Phase 1b study of the gene therapy died and later said he “had more advanced disease with underlying cardiac dysfunction.” The FDA granted accelerated approval last June to Sarepta Therapeutics’ Duchenne muscular dystrophy gene therapy for boys aged 4 to 5. Within the narrow group of patients eligible for Elevidys, demand has been high. The FDA is expected to decide by June 21 on whether to expand the eligible population based on mixed results from a confirmatory study. Last year, Pfizer took a step back from developing early-stage gene therapies, selling a suite of preclinical programs to AstraZeneca. #lucidquest #genetherapy #celltherapy

STAT+ article out this morning on Pfizer’s Duchenne data from World Muscle ~two weeks back. “Perplexing results from Duchenne muscular dystrophy trial raise questions about gene therapies: Pfizer results showed boys did not improve even though target was achieved.” It’s behind a paywall, so quick summary: + Recall, Pfizer’s gene therapy showed no statistically significant improvement in a Phase III Duchenne trial in primary or secondary endpoints BUT it did show an improvement in the microdystrophin production that should, hypothetically, predict a slowing of Duchenne progression.  + Microdystrophin is a surrogate biomarker intended to predict clinical efficacy and was critical to Sarepta’s pathway to market. + The STAT+ authors conclude that this finding may not damn all microdystrophin, but rather the specific version that Pfizer used, still leaving the door open for Sarepta’s microdystrophin to have power (even though it failed its EMBARK primary endpoint) + What does this finding say about using proxies to predict clinical results vs. the clinical results themselves? + And what are the implications for Accelerated Approval for others like RegenxBio and Solid whose planned filings leverage forms of microdystrophin: “The Pfizer data casts doubt on Marks’ nearly unilateral decision. Data presented at the World Muscle Society meeting showed boys who received the drug had produced almost as much microdystrophin on average as healthy individuals produce dystrophin. Yet there was no muscle benefit.” + This one is a bit of a head-scratcher, but STAT goes into strong details about variables in construction, trial length, muscle uptake, and measurement that could lead to Pfizer’s results (or lack thereof). #sarepta #raredisease #duchenne #elevidys #acceleratedapproval #genetherapy

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.

Gene&Cell Therapy >> Florida CNS gene therapy biotech shuts down: Seven-year-old gene therapy startup Lacerta Therapeutics has folded and sold its assets, a board member confirmed to Endpoints News. The University of Florida spinout, based in Alachua, Florida, had forged partnerships with Sarepta Therapeutics, UCB and Eli Lilly’s Prevail. But it “fell victim to a very difficult funding environment in the last couple of years for early stage gene therapy,” said Jackson Streeter, Lacerta board member and director of UF Innovate Ventures, in an email to Endpoints. “Lacerta is not operational and the assets have been sold to an undisclosed buyer,” Streeter said. The biotech downsized last year, and Sarepta terminated a license agreement in May 2023 and took a $30 million impairment loss, according to its annual report from February. A Lilly spokesperson said in an email that the pharma giant has “no information to disclose on this matter.” The company was developing a clinical-stage AAV-based gene therapy for Pompe disease and had other programs for mucopolysaccharidosis type III (or Sanfilippo syndrome), Friedreich’s ataxia, glioblastoma and other CNS indications. Lacerta’s CEO, Edgar Rodriguez-Lebron, left in April and is now CEO of another Florida-based biotech that he co-founded. That company, Andante Biologics, is working on an immunotherapy for chronic stress, according to his LinkedIn bio. The shutdown arrives as multiple large drugmakers pull back from gene therapies and smaller biotechs struggle to secure financing for the complex, capital-intensive class of medicines. A few CNS gene therapy biotechs have still emerged recently, including Latus Bio. Roche’s Spark Therapeutics last month also scrapped development of an experimental Pompe disease gene therapy amid a restructuring. Other drugmakers like Bayer’s AskBio and Astellas are exploring gene therapies for the rare, muscle-weakness genetic disorder. It’s been a particularly rough stretch for the life sciences community in the town of Alachua. Biomanufacturer Resilience laid off workers in the area last year, Endpoints reported in December. Thermo Fisher Scientific has also downsized in the Florida town. Meanwhile, gene therapy biotech Beacon Therapeutics sold its manufacturing facility in the town to Ascend Advanced Therapies earlier this year. #lucidquest #genetherapy #celltherapy

Daily challenge to celebrate advances and good news in the cell and gene therapy space - Day 2: New CNS gene therapy startup Latus Bio using AAVs to deliver CURATIVE treatments for CNS disorders emerged with $54 million in initial Series A financing that will help Latus expand and enter human studies in late 2025. Great to see more financing in the CGT space to deliver curative treatments for unmet medical needs - congratulations! https://lnkd.in/dG8nWqKU 🎯 Aim: 1 post a day to celebrate new scientific advances, partnerships, investments, etc in cell and gene therapies and spread some positivity :) #CGT #genetherapies #celebrate #monthofCGTcelebrations

Gene therapy using #CRISPRCas9 has shown promise in treating hereditary angioedema, reducing symptoms by 95%.   The investigational therapy, NTLA-2002, utilises in vivo CRISPR/Cas9 technology to target the KLKB1 gene, which is responsible for producing plasma prekallikrein.   By editing this gene, the therapy reduces the levels of total plasma kallikrein, effectively preventing angioedema (swelling) attacks.   The results suggest a positive step forward in #genetherapy, offering a more targeted approach in the treatment of genetic disorders whilst hinting at broader applications for #CRISPR based #geneediting in genetic conditions.   Read the study here NEJM Group: https://shorturl.at/uzA01