In Vivo CAR-T Therapies Drive $6.1 Billion in Biotech Acquisitions as Investors Shift from Traditional Cell Therapy Approaches
核心洞察
Major pharmaceutical companies invested over $6.1 billion in in vivo CAR-T therapy (搜索) acquisitions in 2024, with AbbVie (搜索)'s $2.1 billion purchase of Capstan Therapeutics (搜索) leading the surge.
Bristol Myers Squibb (搜索), Gilead Sciences, and AstraZeneca made strategic acquisitions totaling $2.3 billion to secure platforms that eliminate complex ex vivo cell processing and lymphodepletion requirements.
Investors are showing diminished interest in autologous cell therapies while expressing cautious optimism for allogeneic approaches in autoimmune diseases (搜索), according to industry representatives.
The cell and gene therapy sector witnessed a dramatic shift in investment priorities during 2024, with pharmaceutical giants committing over $6.1 billion to acquire companies developing in vivo chimeric antigen receptor (CAR)-T therapies. This represents the highest merger and acquisition deal value in the field since 2020, signaling growing confidence in next-generation approaches that could overcome the manufacturing and safety limitations of traditional cell therapies.
Major Acquisitions Signal Platform Shift
AbbVie (搜索) led the acquisition spree with its $2.1 billion purchase of Capstan Therapeutics (搜索) in June, followed by Bristol Myers Squibb (搜索)'s $1.5 billion acquisition of Orbital Therapeutics (搜索) in October. Gilead Sciences acquired Interius BioTherapeutics (搜索) for $350 million in August, while AstraZeneca invested $425 million upfront for EsoBiotec (搜索) in March, with potential milestone payments reaching $575 million.
These deals reflect a fundamental shift away from the complex manufacturing processes required for approved autologous CAR-T therapies, which involve collecting T cells from each patient, modifying them ex vivo, and re-administering them after patients undergo lymphodepletion with chemotherapy.
"Pharma and investors are moving towards in vivo approaches in the CGT space," said Matthieu Coutet from Sofinnova Partners during a panel discussion at the GenScript Biotech Global Forum London 2024. "These days, pharma are showing very little interest in investing in autologous cell therapy companies."
Two Platform Approaches Emerge
The acquired companies represent two distinct technological approaches to in vivo CAR-T therapy (搜索). Viral vector platforms, exemplified by EsoBiotec (搜索) and Interius, use engineered viral vectors to selectively deliver CAR-T constructs that integrate into T-cell genomes. EsoBiotec's lead candidate, ESO-T01, uses a lentiviral vector coated with nanobodies specific for T cells to deliver a CAR construct targeting B-cell maturation antigen (BCMA (搜索)) on B cells.
The alternative approach uses lipid nanoparticles (LNPs) to deliver RNA-encoded CAR constructs, as developed by Capstan Therapeutics (搜索) and Orbital Therapeutics (搜索). Unlike viral vector platforms, these CAR payloads are transiently expressed rather than integrated into the genome, potentially providing better safety control through dosing regimens.
Autoimmune Applications Drive Interest
The transient expression profile of LNP-RNA platforms has generated particular interest for autoimmune disease applications, where safety requirements are higher than in oncology. Capstan's lead candidate, CPTX2309, an anti-CD19 (搜索) in vivo CAR-T therapy (搜索), entered a phase 1 trial for B cell-mediated autoimmune disorders in June 2024.
Laura Stoppel, partner at RA Capital Management, expressed cautious optimism about allogeneic approaches in autoimmune disease. "I think that's a place where allogeneic actually has the potential to match the efficacy of autologous cell therapy, especially if you don't need long term persistence of these cells," she said.
Orbital Therapeutics (搜索)' lead candidate, OTX-201 (搜索), uses circular RNA encoding a CD19 (搜索)-targeted CAR delivered through targeted LNPs and is currently in studies to enable an investigational new drug application.
Manufacturing Challenges Influence Investment Decisions
The shift toward in vivo approaches addresses significant manufacturing and cost challenges that have limited the broader application of traditional CAR-T therapies. Only 39 patients had received Vertex and CRISPR Therapeutics' approved genome-editing therapy Casgevy by the end of September 2024, highlighting the impact of complex manufacturing requirements.
Daniela Couto, general partner at BioGeneration Ventures, noted that with the development of cost-effective T-cell engagers, "it is difficult to justify investing in cell therapies." She added that investors are largely drawn toward in situ delivery modalities due to cost and complexity of production.
Stoppel emphasized that a biotech's preparedness and investment in manufacturing capabilities is a key consideration when investing, noting there is a need for more innovation to optimize manufacturing processes.
Expanding Beyond Traditional Oncology Applications
Industry experts identified opportunities to expand CGT applications beyond traditional oncology fields. Ophthalmology emerged as a key area, with Couto highlighting Complement Therapeutics' investigation in dry age-related macular degeneration (搜索) and geographic atrophy (搜索) as an example of an investable CGT biotech working in an area of unmet need.
"If we could do a gene therapy, one and done, we would change the way we're treating patients with geographic atrophy (搜索)," Couto said. Panelists also described favorability among investors and pharmaceutical companies for locally administered gene therapies.
Safety Concerns Persist
Despite the investment enthusiasm, challenges remain in the CGT space. Laura Stoppel noted that in vivo gene therapy is still in its infancy with limited data in humans. Safety concerns continue to prompt investor caution, particularly with systemic therapies.
The field has also faced setbacks, with several companies including Takeda, Novo Nordisk, and Galapagos downscaling or discontinuing their cell therapy work. Serious safety issues with Sarepta's marketed gene therapy Elevidys have re-ignited concerns about the toxicities of adeno-associated virus-based therapies.
Nevertheless, the substantial investment in in vivo CAR-T platforms suggests growing confidence that these next-generation approaches can address the manufacturing, safety, and scalability challenges that have limited the broader application of cell and gene therapies.