Lilly, AbbVie, BMS, and Gilead Compete to Invest $14B+ in In Vivo CAR-T Companies
Big Pharma's Acquisition Spree in the In Vivo CAR-T Space
From the latter half of 2025 to the first half of 2026, four major pharmaceutical companies engaged in a series of acquisitions of in vivo CAR-T companies, resulting in a total of over $14 billion in M&A deals. Eli Lilly (LLY) aggressively acquired Kelonia Therapeutics for up to $7 billion (including an upfront payment of $3.25 billion) and Orna Therapeutics for $2.4 billion. AbbVie (ABBV) acquired Capstan Therapeutics for $2.1 billion, Bristol Myers Squibb (BMY) acquired Orbital Therapeutics for $1.5 billion, and Gilead's (GILD) Kite acquired Interius BioTherapeutics for $350 million. This strategic move aims to overcome the manufacturing complexity and high costs (approximately $400,000 to $500,000 per patient) associated with existing ex vivo CAR-T therapies. In vivo CAR-T, which directly reprograms T cells within the body, has emerged as a key to enabling large-scale production and expanding accessibility.
Seven Phase 1 Clinical Trials Underway Simultaneously, with Kelonia's 100% Response Rate Drawing Attention
Currently, seven in vivo CAR-T programs are in Phase 1 clinical trials. Kelonia's KLN-1010 (anti-BCMA, multiple myeloma) demonstrated a 100% overall response rate in the inMMyCAR study, which was presented at ASCO 2026, justifying Lilly's $7 billion acquisition. Interius' INT2104 (anti-CD20, B-cell malignancies, NCT06539338) initiated its first-in-human clinical trial in Australia in October 2024, and Umoja Biopharma's UB-VV111 (anti-CD19, NCT06528301) received FDA Fast Track designation. Capstan's CPTX2309 (anti-CD19, autoimmune diseases) also entered Phase 1 in June 2025, indicating a trend of expanding indications from hematological malignancies to autoimmune diseases.
Three Main Delivery Platforms: Lentiviral Vectors, LNP-mRNA, and Circular RNA
The technological differentiation in in vivo CAR-T lies in the delivery platform. Kelonia, Umoja, Interius, and Vyriad use lentiviral vectors to permanently insert the CAR gene into the patient's T-cell genome. Capstan (AbbVie) employs targeted lipid nanoparticles (LNPs) to deliver mRNA, inducing transient CAR expression in CD8+ cytotoxic T cells. Orna (Lilly) and Orbital (BMS) utilize a combination of circular RNA and LNPs to achieve more sustained expression. CPTx, a spin-off from the Technical University of Munich (TU Munich), is developing a unique non-viral platform based on immune-silent single-stranded DNA (ssDNA) vectors. The differences in CAR expression duration, immunogenicity, and off-target effects among these platforms will be key determinants of clinical success.
Vyriad and CPTx, Remaining Independent, Emerge as Potential Acquisition Targets
Among the eight companies, Vyriad and CPTx remain independent and have not been acquired by big pharma. Vyriad, founded in 2015 by scientists from the Mayo Clinic, achieved 100% tumor elimination in a multiple myeloma mouse model within 28 days in preclinical studies of its anti-BCMA candidate, VV169, and completed a $85 million Series B financing round, aiming to submit an IND application to the FDA and initiate Phase 1 trials in 2026. CPTx raised $100 million in a Series C round in January 2025 and is developing a dual-targeting non-viral in vivo CAR-T therapy targeting CD19/CD20 for the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). As big pharma continues to compete to secure in vivo CAR-T portfolios, these two companies are attracting investor interest as potential M&A or IPO candidates.
The in vivo CAR-T market is projected to grow from $650 million in 2025 to $10.8 billion in 2035, with a CAGR of 32.5%. This growth potential, coupled with the ability to structurally replace the existing ex vivo CAR-T market (approximately $5 billion to $9 billion in 2025, centered around Yescarta, Carvykti, and Breyanzi), explains the $14 billion+ M&A wave from 2025 to 2026. This wave indicates that in vivo platforms have moved beyond preclinical stages and are entering clinical validation, as demonstrated by the 100% response rate of Kelonia's KLN-1010 at ASCO 2026. Eli Lilly (LLY) has committed a total of $9.4 billion by acquiring Kelonia ($7 billion) and Orna ($2.4 billion), securing a dual platform of lentiviral vectors and circular RNA. AbbVie (ABBV) has built a dual-track approach by acquiring Capstan ($2.1 billion) and licensing Umoja (up to $1.44 billion), covering both LNP-mRNA and lentiviral vector technologies. The independent companies, Vyriad ($85 million Series B) and CPTx ($100 million Series C), are on track to submit IND applications in 2026, making them potential targets for future M&A events or IPOs, which are key points of interest for investors.
Source: Labiotech (rss)
https://www.labiotech.eu/best-biotech/in-vivo-car-t-companies/