With ASGCT25 in the rearview mirror, some DHC Horses wrote up a brief review of their take-homes from the meeting.
Kim Benton, Ph.D., Master Principal and Head of Regulatory:
The session “FDA’s START Pilot Program in Action: Insights from Year One” held on the afternoon of May 15th at 2025’s ASGCT provided a nice overview of this FDA initiative to accelerate the development of rare disease therapeutics. Representatives from Neurogene, Moderna, and Myrtelle, three of four companies with CGT rare disease programs selected for the START pilot, spoke about their experiences.
The intent of the START pilot was to facilitate more efficient development of potentially life-saving therapies for rare disease indications and generation of high-quality compelling data to support a future marketing application. The pilot aims to achieve this goal via enhanced communication between FDA and the selected pilot participants. The speakers described a regular cadence of meetings with the FDA review team, prospectively scheduled on a quarterly basis. The logistics of these meetings sounded typical of formal meetings with FDA, in that the Sponsor prepared and submitted a briefing package, FDA provided preliminary responses in advance of the meeting, and based on these responses the Sponsor could select the key issues to prioritize for discussion at the meetings. FDA issued final meeting minutes. While the speakers did not provide specifics of their FDA meetings, they did note that topics included clinical study design, appropriate control group and patient population, statistical analysis, product characterization and other CMC topics, and overall discussion of flexible approaches that could be taken in development.
The pilot participants noted that FDA was receptive to ad hoc teleconferences and email exchanges as needed between the quarterly meetings. It was mentioned that the communication was a two-way street, with FDA communicating questions to the sponsors as they arose during review. The resource commitment was also noted to be two-way. The speakers described that preparation of meeting briefing packages was a nearly continuous activity with the frequent cadence of meetings with FDA. The speakers characterized the START pilot as constructive, efficient, and an overall well-run program. They expressed hope that the program will be continued and expanded for all rare disease therapeutic development.
Sam Blackford, Ph.D., Consultant:
Attending ASGCT in New Orleans this year 100% lived up to expectations. On a personal level, it was amazing to see IND-enabling nonclinical data and subsequent clinical trial updates presented by clients I have had the opportunity to support. Seeing their achievements presented to our shared scientific community filled me with collective pride. Most importantly for myself, the conferenced offered another opportunity to remain up-to-date on the latest technologies, innovations, model systems, and regulatory precedents that are vital in support of our clients. ASGCT attendance provided the perfect environment to get a deeper understanding of the latest developments in CGT.
Particular meeting highlights for me included:
(1) “Next Generation Strategies For Evading Immunity in Stem Cell Therapies” in which both unique and overlapping cell engineering strategies to prevent immune recognition were presented. Talks also included discussions around “kill switches” and the development on nonclinical humanized models with immune systems “primed” to respond against a non-engineered product.
(2) “Organoids and iPSC Disease Modeling for Drug Discovery” in which notable topics were the development of human iPSC-based models of the blood-brain barrier in which to test novel engineered AAV variants, and how in vitro live phase imaging pipelines can enable medium throughput screening of compounds which may be neuroprotective or support axon regeneration.
(3) “Lipid Nanoparticles” whereby it was presented through combining transposon-based DNA delivery systems with non-viral nanoparticlesthat there is potential to treat Hemophilia A, with the nonclinical data demonstrating that near-normal levels of Factor VIII protein could be achieved in both juvenile and adult murine models. Moreover, in this session, proprietary intracellular trafficking agents were shown to enhance DNA delivery when integrated into lipid nanoparticles through improving DNA protection and enhancing endosomal escape.
(4) Outside of the scheduled sessions, the ASGCT poster hall offered an exciting glimpse into the future with countless exciting nonclinical projects being presented. I was particularly excited to see how deep learning-trained codon optimization algorithms can enable greater expression and secretion, albeit in vitro, of therapeutic transgenes such as alpha-1 antitrypsin. I eagerly anticipate ways in which this and similar approaches can be deployed to develop more efficacious therapeutic products.
Catherine Colandro, Senior Consultant:
With my process engineering background, I was captivated by Akadeum Life Sciences' unveiling of their enhanced microbubble technology while attending the 2025 ASGCT Annual Meeting in New Orleans in May. This innovation promises to revolutionize cell therapy manufacturing by offering a gentle, scalable alternative to traditional magnetic separation methods. Their microbubble-based approach enables seamless integration into existing workflows, whether manual or automated, reducing both operational costs and physical footprint. A highlight was the presentation at one of the Tools and Technology forums, emphasizing how microbubbles can replace magnetic systems to yield higher purity T cells more efficiently. Additionally, they demonstrated integration of the microbubble separation technology into several different platforms including the Rotea, G-Rex®, the Cocoon®, and even within a cell culture bag. They showcased improved throughput and consistent cell viability, crucial for CAR T therapy applications. Akadeum's booth also provided hands-on demonstrations, illustrating the technology's adaptability across various systems and applications. This microbubble technology stands out as a significant advancement in cell separation, offering a more scalable, efficient, and cost-effective solution for therapeutic manufacturing. Their commitment to enhancing cell therapy processes is evident, and I look forward to seeing how this technology shapes the future of cell therapy processes.
Elizabeth Figueroa, Ph.D., Senior Consultant:
I've been studying and keeping a close eye on non-viral vectors since beginning my Ph.D in 2010 in a nanobiophotonics laboratory. By the time I left graduate school in 2015, LNPs for gene therapy were still not commercially approved and I made the choice to continue to pursue nonviral gene therapy vectors as my specialty because I believed they would be transitioning into the clinic imminently. In the years since, I have seen LNPs gaining significant momentum as evidenced by their use in vaccines (Spikevax, Comirnaty), and importantly via systemic routes of administration for gene silencing (Onpattro) and delivery of next generation genome editing technologies (currently in clinical trials).
I kicked off the week of ASGCT 2025 in New Orleans having just published a white paper titled "The next frontier of in vivo gene therapy: are LNPs the new AAV?" Imagine my delight when one of the biggest splashes of the conference centered LNPs: the N-of-1 personalized base editing therapy for baby KJ Muldoon via an LNP delivery vector. Dr. Kiran Musunuru (of the University of Pennsylvania School of Medicine) and Dr. Rebecca Ahrens-Nicklas (of Children's Hospital of Philadelphia) provided ASGCT attendees with a one-two punch, walking us through their groundbreaking work in two sessions. The sheer speed with which this therapy was developed, screened, optimized, and manufactured was hugely encouraging to behold, a testament to the possibilities available when multiple academic, industry, and regulatory agency stakeholders collaborate efficiently towards a common goal. It also belies the benefits of non-viral vectors relative to their viral counterparts; I truly do not think this would have been possible in the same timeframe with a viral vector due to the complexity and duration of viral vector manufacturing processes.
I also appreciated the messaging that Musunuru and Ahrens-Nicklas provided around mutational discrimination: the idea that developing personalized gene therapies for patients is not possible in many parts of the world due to the extensive uncatalogued variants for most patients worldwide. While it is true that the manufacturing cost, complexity, and cold chain make LNPs well suited for global reach, mutational discrimination is a hurdle we must overcome in order to truly globalize the reach of non-viral gene therapies.
Christina Fuentes, Ph.D., Senior Consultant:
My biggest takeaway from ASGCT 2025 was the intersection of the latest and greatest advancements in research and emerging tech with the counterpoint of patient experience and advocacy. It’s so easy to focus on the approval of a therapy or clinical product but from the patient’s point of view, that is just the beginning. That larger view of the interconnection of the work that we’re doing and the ultimate recipients of that work—and ways in which we can strive for expanded patient access—really struck me.
One session that highlighted that particularly well was obviously the n-of-1 baby KJ news (timed nearly to the moment with the release of the NYT article on the subject). In part this success strikes me as due to the investigators having streamlined their screening and optimization of the product. Their collaboration with industry (Danaher, for example) also increased their ability to move swiftly while developing safe and efficacious products. I saw this as an adaptation to the climate and changes in funding and dreaming big (or very small, on an individual scale) if streamlined efficiencies take hold.
I saw some intertwining of these goals with a panel discussion on “Ensuring Diversity and Inclusion in Later Stage Cell and Gene Therapy Development,” chaired by Dr. Rouce, associate professor at Baylor College of Medicine, along with Pat Furlong from the Parent Project Muscular Dystrophy, PPMD and then Dr. Olajide Williams, of Columbia University.
Much of that discussion was centered on expanding patient access, the role that advocacy groups play, and the unimaginable ethical dilemmas that can come into play. (A brutally hard story, for example, was of parents with twins, both of whom had muscular dystrophy. Funds had been raised but it was only enough to treat one of the children. I can’t imagine being in that family or on that care team and being faced with such a situation.) Dr. Williams then spoke about participant-centered research engagement and how bring community health workers into the discussion to engage communities, build trust, and provide good follow-up and communication so as to transition successfully to the practitioner who will administer the clinical products/treatment.
The pattern I experienced was about perspectives that went beyond what I’d personally considered before: both in terms of opportunity and oflimitations. It was a poignant learning experience that I think will help further round out my ability to provide quality support to future clients and the patients who are the ultimate recipients.
