Blog | 4/29/2025

State of CGT and What to Look for at ASGCT 2025

By Ned Wydysh, PhD, Vivek Mittal, PhD, Alicia Shields, PhD, Andrew Chen, Dorian Cohen, Younan Li, PhD

As we head into the 2025 ASGCT Annual Meeting in mid-May, the breadth of presentations, abstracts, and posters can be daunting. Health Advances’ Cell and Gene Therapy practice highlights several of our major areas of interest within the field and the corresponding sessions at ASGCT to make navigating the conference more manageable.

Commercial Uptake Challenges

Following the initial excitement around cell and gene therapy with the first approvals of CAR-T and AAV gene therapy programs, the field has produced more tempered enthusiasm for these novel modalities’ future roles as standards of care for broader populations. The early commercial uptake challenges for many of the approved products have been well documented and are a result of a combination of factors including market access, logistical, and manufacturing challenges, with the strongest predictor of uptake being the product’s ability to address specific patient unmet needs (Figure 1). As the CGT field evolves, there is increasing recognition that new approaches are needed to address patient needs and transform care outside of the initial applications. That strong potential in several major technology and therapeutic areas continues to be a theme in the field and will be in focus at ASGCT 2025.

Figure 1

CAR-T for Autoimmune Diseases

CAR-T therapies have demonstrated remarkable efficacy in hematologic malignancies by targeting pathways associated with malignant B cells, achieving objective response rates of up to 80-90%+. Since 2017, six CAR-T products have been approved, marking a groundbreaking advancement in oncology. As competitive pressure in oncology intensifies, many manufacturers are exploring CAR-T in other therapeutic areas, most notably in autoimmune diseases, where autoreactive B cells are often the culprits behind a multitude of conditions. For many patients who struggle with insufficient disease control, long-term immunosuppression, or the need for frequent biologic injections, CAR-T therapies present the possibility of a highly efficacious single-treatment solution.

Several manufacturers are already leading the way in developing CAR-T therapies in immunology. For example, Kyverna Therapeutics is investigating KYV-101, an autologous CD19 CAR-T therapy, for conditions such as Stiff-Person syndrome, myasthenia gravis (MG), multiple sclerosis, lupus nephritis, and systemic sclerosis, highlighting CAR-T’s broad potential in B cell-driven neuroinflammatory diseases. Similarly, Cabaletta Bio is evaluating its lead candidate CABA-201 in systemic lupus erythematosus, myositis, systemic sclerosis, and generalized MG, with potential applications in a broader portfolio of autoimmune diseases. Early findings from last year suggested that both assets effectively depleted B-cells and improved biochemical markers as well as clinical outcomes. Additionally, Cartesian Therapeutics recently announced positive 12-month data from its ongoing Phase 2b trial of Descartes-08, an autologous CAR-T product targeting BCMA, in generalized MG.

Stem Cell Therapies for Difficult-to-Treat Conditions

Stem cell therapy, also known as regenerative medicine, has a long history dating back to the late 19th century. The FDA has approved several stem cell-based products for hematology and dermatology (e.g., wound care) use over time. Today, stem cell therapies are emerging as a promising approach for diseases where traditional treatments have been considered insufficient.

Several companies are at the forefront of developing stem cell therapies for difficult-to-treat conditions. For example, Sana Biotechnology announced positive clinical results in January 2025 from its first-in-human Type 1 Diabetes (T1D) study using islet cell transplantation without immunosuppression. While the FDA approved the first allogeneic cell therapy for T1D back in 2023, Sana’s study involved transplanting allogeneic primary islet cells engineered with Sana’s hypoimmune platform (HIP) technology. Results demonstrated HIP-engineered islet cells can avoid immune detection and function properly after intramuscular transplantation. This provides promising evidence for a new treatment approach for T1D without the need for immunosuppression.

Another example is BlueRock Therapeutics, a leading engineered cell therapy company that Bayer fully acquired in 2019 at a company value of ~$1B. BlueRock’s lead asset, bemdaneprocel, is currently being investigated for treating Parkinson’s disease. This therapy utilizes allogeneic pluripotent stem cells to replace lost dopaminergic neurons, with the aim of restoring motor function. Following a positive Phase I trial that demonstrated a favorable safety profile and encouraging trends in motor symptom improvement at 24 months, Bayer and BlueRock are advancing bemdaneprocel to Phase III in the first half of 2025. This trial will assess the therapy’s efficacy and safety in 102 participants with moderate Parkinson’s disease.

Partnerships Between Cargo Companies and Non-Viral Delivery Companies

Gene therapies have emerged as a groundbreaking approach to treating genetic diseases, offering hope for patients with conditions previously thought untreatable. At the heart of gene therapy lies the transfer of genetic material into disease cells to correct genetic defects. However, this process is far from simple. Successful gene therapy development requires overcoming numerous biological barriers, both extracellular and intracellular. These challenges include enzyme degradation, serum protein interactions, electrostatic repulsion between genes and cell membranes, the innate immune system, and obstacles within the cells themselves, such as endosomal escape, transport barriers, and the precise release of the genetic material.

Viral vectors have long been used in gene therapies due to their natural ability to deliver genetic material into target cells. Their high transduction efficiency, or ability to introduce the gene into cells, has made them a popular choice for researchers, resulting in higher success rates in clinical trials. However, despite their effectiveness, viral vectors come with significant safety concerns. These include immune responses against the viral vector, potential overexpression of the transgene product, an increased risk of mutagenesis due to unintended genomic edits, and other immunogenic risks. These safety concerns limit the patient populations that can safely receive gene therapies and make repeated dosing challenging, preventing gene therapies from reaching their full potential.

To overcome these limitations, the field of gene therapy is actively exploring safer and more efficient ways to deliver genetic material. A promising area of development is the use of non-viral vectors, which bypass some of the issues associated with viral vectors. Non-viral delivery systems can be broadly categorized into two types: non-viral delivery systems that use engineered vectors, and physical delivery methods.

Non-viral delivery systems employ various types of vectors, such as extracellular vehicles, lipid nanoparticles, gold nanoparticles, and polyplexes, to carry genetic material. Physical delivery methods, on the other hand, include techniques like electroporation, ultrasound energy, or direct microinjection of the genetic material into cells. While these non-viral methods offer significant advantages, they are not without their own set of challenges.

A common limitation across many non-viral delivery technologies is their relatively low transfection efficiency and stability. Unlike viral vectors, which have naturally evolved to overcome biological barriers and effectively deliver their genetic payload, non-viral methods often require more sophisticated technologies to achieve similar outcomes. As a result, fewer biotech companies have the resources to develop non-viral delivery systems in-house, leading to an increase in partnerships and collaborations in the field.

This need for advanced delivery systems has resulted in several high-profile partnerships recently aimed at optimizing gene therapy technologies. For instance, in September 2024, MaxCyte entered a strategic platform license agreement with Kamau Therapeutics. This partnership allows Kamau to utilize MaxCyte’s flow electroporation technology and ExPERT platform to optimize the production of CRISPR-Cas9-based therapies for sickle cell disease. Similarly, in December 2024, the epigenetic editing startup Chroma Medicine merged with Nvelop Therapeutics, securing $75 million in funding to develop in vivo genetic medicines targeting chronic hepatitis B and D. This merger gives nChroma access to Nvelop’s two non-viral delivery platforms, DLVR-X and DLVR-M.

In early 2025, Vertex Pharmaceuticals and Orna Therapeutics announced a three-year collaboration to develop next-generation gene therapies for sickle cell disease and transfusion-dependent beta-thalassemia. This collaboration will leverage Orna’s lipid nanoparticle technology to improve the efficiency of gene editing, potentially addressing the limitations of existing therapies.

The momentum for non-viral gene therapy technologies continues to grow. More biotech companies are now emphasizing novel non-viral delivery systems, and an increasing number of gene therapies using these platforms are entering clinical trials. Companies like Orna Therapeutics, Generation Bio, Arcturus, and ReCode Therapeutics are all utilizing lipid nanoparticle (LNP) technologies in their gene therapies. Aera Therapeutics has developed two distinct delivery platforms, one using LNPs and the other using polymer nanoparticles (PNPs). nChroma is focusing on virus-like particles, while Genedit employs polymer nanoparticles. SonoThera is developing the first ultrasound-mediated non-viral gene delivery platform, and Inomagen and MaxCyte use electroporation for delivery.

As more biotech companies recognize the potential of these non-viral systems, we can expect to see increased collaboration between "cargo" and "delivery" companies. These partnerships will be instrumental in developing innovative, safer, and more effective gene therapies, expanding the possibilities of genetic medicine for patients worldwide.

Optimizing for Success: Cell and Gene Therapy Companies' Reprioritized Pipelines and Narrowing Focus

In recent months, cell and gene therapy companies have been actively reprioritizing their pipelines and shifting their focus to optimize resources and address emerging opportunities. This trend is evident in the strategic decisions made by several companies:

Editas has halted development of its lead ex vivo sickle cell treatment, Reni-cel.. Like the two sickle cell gene therapies approved in 2023, Reni-cel required extracting a patient’s blood cells, editing them, and then reinfusing. Editas has decided to focus on a new sickle cell program, which involves editing a patient’s cells in vivo, eliminating the need for expensive manufacturing or high dose chemotherapy.

Intellia Therapeutics, attempting to harness CRISPR-based gene editing technologies, has discontinued NTLA-3001, a Phase 1/2 program for alpha-1 antitrypsin deficiency (AATD). Intellia will prioritize resources around its two Phase 3 gene therapy candidates, NTLA-2002 and Nex-z, targeting hereditary angioedema (HAE) and transthyretin (ATTR) amyloidosis, respectively.

Galapagos has fully embraced oncology cell therapy and separated from a new spin-off company, "SpinCo," which will develop a variety of medicines independently. Galapagos will focus on its lead CAR-T candidate, GLPG5101, which has demonstrated an encouraging efficacy and safety profile in patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL), while SpinCo will be focused on building a pipeline of medicines through strategic business development transactions in collaboration with Gilead.

4D Molecular Therapeutics is cutting two clinical programs and reallocating resources to launch late-stage studies for its eye disease gene therapy, 4D-150. The discarded programs include 4D-110 for choroideremia and 4D-125 for X-linked retinitis pigmentosa. 4DMT is also cutting off further investment for three more programs, including ongoing phase 1/2 trial assessing 4D-310 for Fabry disease-related cardiomyopathy, preclinical 4D-175 in geographic atrophy, and 4D-725 in AATD lung disease. Funds will be used for pre-commercialization activities for 4D-150 in wet AMD and to push it into late-stage testing for diabetic macular edema (DME).

Following a pipeline review, Astellas Pharma halted development of its autologous CAR-T program, ASP2802, aimed at CD20-positive B-cell lymphomas. ASP2802 was developed using Xyphos’ technology, whom Astellas paid $120MM upfront to acquire in 2019. Despite the decision to stop development of ASP2802, Astellas continues to make cell therapy deals with Xyphos and work on a range of cell therapies for cancers, vascular disease, autoimmune diseases, and more.

Notably, there has been an increase in deals focused on gene therapies for several rare CNS disorders:

Novartis acquired Kate Therapeutics to strengthen its position in gene therapy and CNS innovation. Kate Therapeutics’ primary programs include preclinical candidates for Duchenne muscular dystrophy (DMD), facioscapulohumeral dystrophy (FSHD), and myotonic dystrophy type 1 (DM1).

In addition, Sarepta Therapeutics is acquiring worldwide licensing rights to seven of Arrowhead Pharmaceutical’s programs. The deal gives Sarepta access to several clinical stage CNS programs including ARO-DUX4 for FSHD, ARO-DM1 for DM1, and ARO-ATXN2 for spinocerebellar ataxia 2 (SCA2) and pre-clinical programs including ARO-HTT for Huntington’s disease, ARO-ATXN1 for SCA1, and ARO-ATXN3 for SCA3. All the programs included in the deal were developed using Arrowhead’s TRiM (targeted RNAi molecule) platform. This platform delivers small interfering RNA (siRNA) to various tissue and cell types, enhancing RNA interference and effectively reducing the expression of target genes.

Capsida Biotherapeutics announced that AbbVie has exercised an option for the first neurodegenerative disease program under their collaboration. AbbVie opted in based on data showing that Capsida’s adeno-associated virus (AAV) capsids could deliver AbbVie’s gene therapy to primates' brains. In addition to a $40 million licensing payment, Capsida can receive development and commercial milestones along with royalties on future sales. The milestone is part of a strategic collaboration and licensing agreement announced in 2021, in which Capsida and AbbVie partnered to develop targeted genetic medicine therapies for three neurodegenerative diseases.

Emerging Epigenetic and RNA Editing Programs

Epigenetic editing companies, such as Tune Therapeutics, are pioneering the use of epigenetics to modulate gene expression. This strategy circumvents the need to directly cut or replace DNA, opting instead to deactivate or reactivate genes to treat various diseases. This approach is seen as less invasive compared to DNA-cutting technologies like CRISPR, which can potentially cause DNA damage.

In January, Tune Therapeutics received regulatory approval in New Zealand and Hong Kong to conduct human trials for its epigenetic silencing therapy, Tune-401, which targets chronic hepatitis B. This therapy aims to prevent the production of the hepatitis B virus by epigenetically altering gene expression.

Moonwalk Biosciences is building complete methylation maps of T cells to identify new targets with its EpiRead platform and applying its epigenetic editing technology, EpiWrite, to developing novel multiplexed editing therapies.

Meanwhile, nChroma Bio, formed from the merger of Chroma Bio and Nvelop Therapeutics, is also exploring a potential treatment for hepatitis B.

Epicrispr Biotechnologies, another frontrunner in epigenetic editing, is harnessing the capabilities of CRISPR without the need for DNA cutting. The company is developing treatments for several conditions including FSHD, AATD, and heterozygous familial hypercholesterolemia (HeFH). Its lead program, EPI-321, seeks to address the core molecular mechanisms of FSHD by restoring methylation to the D4Z4 region of chromosome 4, thereby halting the toxic expression of the DUX4 gene. Preclinical studies have shown that EPI-321 effectively suppresses the pathological expression of the DUX4 gene and reduces muscle cell death.

RNA editing, which holds potential advantages over DNA editing, is also in the spotlight as an emerging therapeutic modality. Its more transient treatment effect could help significantly expand addressable indications outside of more severe monogenic diseases toward those with variable symptoms or severity, requiring dosing flexibility or acute, nonpermanent treatment courses. While RNA editing therapies are still quite early in development, several notable companies at the forefront are making progress across early pipeline programs.

Wave Life Sciences’ RNA editing therapy is in clinical development for AATD, with positive initial results announced from treatment of the first two patients in October. Shape Therapeutics is developing therapies for Rett syndrome, Stargardt disease, and AATD in addition to CNS-targeting therapies through a partnership with Roche. Ascidian Therapeutics is currently in Phase I for Stargardt disease and other ABCA4-related retinopathies, while ProQR is expected to enter the clinic in 2025 with its first program targeting cholestatic diseases.

ASGCT 2025 Sessions

There will be high profile sessions focusing on each of these topics at the ASGCT Annual Meeting in New Orleans, with a considerable amount of attention on advancements in gene editing technologies and program readouts. These are highlighted below:

Wednesday May 14^th:
- 1:30pm Scientific Symposium discussion on hypothetical risks of off-target editing
Thursday May 15^th:
- 8:00am Scientific Symposium on Cell and Gene Therapies for Autoimmune Disease including presentations by Cabaletta Bio and Orna Tx
- 8:00am Scientific Symposium on Advances in Genome Editing with Large DNA Insertion Technologies
- 1:30pm Oral Abstract Session on Epigenetic and RNA Editing including presentations by Reforgene Medicine and Wave Life Sciences
- 1:30pm Oral Abstract Session on Novel Approaches to Gene Targeting and Correction
- 3:45pm Oral Abstract Session on CAR-T Innovations in Autoimmune, Infectious Disease, and Allergy including presentation by GentiBio, Capstan Therapeutics, and Sanofi
- 3:45pm Oral Abstract Session on Novel Therapeutic Gene Editing Applications
Friday May 16^th:
- 8:00am Scientific Symposium on Gene Therapy and Gene Editing Approaches for Human Disease
- 8:00am Oral Abstract Session on Emerging Delivery Platform for In Vivo Gene Editing
- 1:30pm Clinical Trials Spotlight Symposium
- 1:30pm Scientific Symposium on Next Generation Strategies for Evading Immunity in Stem Cell Therapies with presentations by Sana Biotech and Aspen Neuroscience
- 3:45pm Scientific Symposium on Targeted Nanosystems for Gene Transfer and Editing: Beyond Delivery to the Liver

Top Open Questions in CGT

We ask and are asked many questions surrounding cell and gene therapy. Here are a few we hear a lot in our conversations with physicians, payers, drug makers, and investors.

How much data is needed to demonstrate clinically relevant durability?
In theory, cell and gene therapies are “one-time” therapies designed to last, but increasingly, we’ve seen that assumption challenged. There is now emerging evidence that patients treated with Zolgensma could still benefit from additional chronic therapy. Some clinicians also observed that liver cells, a common target of gene therapy, are known to turnover, prompting questions around the longevity of exogenous genes. Confidence in durable effect is one of the tenets behind the value proposition and the clinical risk-benefit assessment. It’s also a key assumption behind the high price tags of gene therapy, often at multiples of the annual price of chronic therapy. One thing is certain: any data supporting the durability of effect, even from first-in-human trials, will be closely watched by all stakeholders.
Will outcomes-based agreements take root?
Outcomes-based agreements are often suggested as a potential solution to the efficacy and durability uncertainties surrounding cell and gene therapy. Sickle cell and beta thalassemia appear to be the first indications where outcomes-based agreements have gained the most traction. However, whether this model could be extended to other indications, including commercial and Medicare populations, remains to be seen. Proponents champion it as a win-win by providing patients access to therapy and shifting some of the risks traditionally borne by payers. Anecdotally, we’ve also heard some pushback from traditional commercial payers around the challenges of tracking patient outcomes and the high patient turnover rate (average patient only stays on a commercial plan for ~3 years, rendering long-term outcomes tracking impossible).
How will cell and gene therapy perform in competitive markets?
Luxturna had the whole RPE65 market to itself, but RPE65 was only a moderately sized market. Cell and gene therapies today often find themselves sharing a slice of a larger and competitive pie. They try to dethrone chronically administered incumbents with more convenient and sometimes more efficacious solutions. But how much competitive advantage is needed to compete effectively in crowded markets? It’s still the early days of gene therapies “in the big leagues,” but we are already starting to notice leaders and laggards in competition with traditional modalities.
Gene therapies could compete with each other too. Hemophilia and sickle cell disease are the first two markets with multiple gene therapies competing head-to-head against each other. How would a “first mover advantage” in gene therapy differ from that of traditional modalities? Regardless of their speed to market, cell and gene companies can employ a range of strategies to make the most out of their positions.
How will patients react, when given a choice?
The slower than expected uptake of gene therapy in hemophilia is likely influenced by physician enthusiasm, but how much of the decision was physician vs patient-driven? We often hear from physicians that when it comes to brand new modalities like gene therapy, given so many unknowns, they present it as an option and let the patient drive the decision making when possible. In certain indications, patients are extremely knowledgeable about their condition and play a significant role in the shared decision-making process around therapy adoption. Patient market research has evolved to be an integral component in demand studies in cell and gene therapy, especially when multiple competing options are on the table. It’s more important than ever for manufacturers to understand patient needs and position product value drivers to win the hearts of patients.

Ned Wydysh, PhD is a Vice President and co-leader of Health Advances’ Oncology and Cell and Gene Therapy Practices.

Vivek Mittal, PhD is a Partner, Managing Director, and co-leader of Health Advances’ Oncology and Cell and Gene Therapy Practices.

Alicia Shields, PhD is an Engagement Manager within the Health Advances Cell and Gene Therapy Practice.

Dorian Cohen is a Consultant and team leader within the Health Advances Cell and Gene Therapy Practice.

Andrew Chen is a Consultant and team leader within the Health Advances Cell and Gene Therapy Practice.

Younan Li, PhD is a Senior Advanced Analytics Specialist within the Health Advances Cell and Gene Therapy Practice.