In vivo CAR-T: Is there a growing shortage of target antigens?
Apr 29,2026
Following its acquisition of Orna Therapeutics for up to $2.4 billion this February, pharmaceutical giant Eli Lilly recently announced another $7 billion takeover of Kelonia Therapeutics, a biotech focused on the in vivo CAR-T track.
This marks the latest high-value deal demonstrating big pharma’s willingness to pay staggering premiums for in vivo CAR-T technologies.
In August 2025, Gilead Sciences acquired in vivo CAR-T developer Interius BioTherapeutics for $350 million. Two months later, its subsidiary Kite Pharma struck a $1.6 billion collaboration with Progen Biotech. In the same year, AbbVie purchased Capstan Therapeutics for $2.1 billion, BMS acquired Orbital Therapeutics for $1.5 billion, and AstraZeneca sealed a $1 billion buyout of EsoBiotec.
Despite this acquisition frenzy, an analyst at research firm Pitchbook projects that the pace of in vivo CAR-T transactions will slow down.
This slowdown stems not from fading pharmaceutical interest, but from a severe shortage of high-quality targets with viable acquisition value.
1、Worth the Premium
Traditional autologous CAR-T therapy requires extracting patients’ own T cells, genetically engineering them to target cancer, and infusing the modified cells back into the body. By contrast, in vivo CAR-T directly generates functional CAR-T cells inside patients via gene editing technologies.
The immense potential of in vivo CAR-T fully justifies substantial upfront payments from pharmaceutical companies for early-stage R&D programs. Critically, this therapeutic modality is poised to expand from oncology to autoimmune diseases, unlocking far broader value potential.
Analysts at Leerink Partners note that large pharmaceutical enterprises are pursuing these acquisitions primarily as a defensive strategic move. Having invested heavily in building high-barrier CAR-T technology platforms, industry leaders must embrace disruptive innovation proactively rather than falling behind.
Gilead’s layout typifies this strategy. Kite Pharma’s two commercialized autologous CAR-T products, Yescarta and Tecartus, have achieved solid market success. However, breakthroughs in in vivo CAR-T technology could directly disrupt the market standing of Gilead’s flagship cell therapy assets.
Meanwhile, intensifying industrial competition has driven continuous sales declines for Gilead’s two marketed CAR-T drugs. Facing both internal pressures and external headwinds, investing in next-generation cutting-edge technologies has become essential for the company to break through bottlenecks.
For late entrants like Eli Lilly, the core priority is to build a diversified therapeutic pipeline to hedge industry uncertainties. “In cell therapy, companies often overestimate their own understanding and control capabilities. Diversified mergers, acquisitions and partnerships effectively mitigate R&D risks,” the analyst added.
Clinical data will ultimately determine the trajectory of this track. Kelonia, newly acquired by Lilly, released clinical data on four patients with relapsed and refractory multiple myeloma late last year. The results delivered a 100% objective response rate, with CAR-positive cells accounting for 22% to 85% of total CD3+ lymphocytes, alongside the formation of memory CAR-T cells. In terms of safety, only Grade 2 cytokine release syndrome (CRS) was reported, with no observed immune effector cell-associated neurotoxicity syndrome (ICANS).
Nevertheless, even with the favorable low-toxicity profile shown in early trials, the long-term safety consistency needs to be validated in larger patient cohorts and subsequent clinical studies.
UB-VV111 from Umoja Biopharma and a novel in vivo CAR-T candidate from Legend Biotech are also under widespread spotlight. UB-VV111 is currently in Phase I clinical trials for patients with CD19-positive B-cell malignancies, while Legend Biotech’s candidate has completed first-in-human dosing.
Analysts caution that the industry tends to overreact to small-sample clinical data. Early patients receiving novel therapies are not universally representative; they typically receive enhanced monitoring, premium medical resources and top-tier physician care, limiting the generalizability of such outcomes.
In addition, current CAR-T therapies are mostly administered in intensive care units. The ability of in vivo CAR-T to shift toward outpatient administration will serve as a key milestone for widespread clinical adoption.
2、Dearth of Quality Targets
Two pharmaceutical giants, Johnson & Johnson and Novartis, remain notable absentees in the in vivo CAR-T landscape with no relevant pipelines to date, yet high-quality acquisition targets have become exceedingly scarce.
Seattle-based Umoja Biopharma has emerged as one of the most sought-after biotechs in the sector. The company has two clinical-stage candidates in its portfolio. UB-VV400/410, targeting CD22 for autoimmune diseases and non-Hodgkin lymphoma, is currently in Phase I clinical development in China. This program is co-developed with IASO Therapeutics. Under a 2024 collaboration agreement, Umoja leverages IASO’s clinically validated CAR sequences combined with its proprietary VivoVec platform to advance in vivo CAR-T candidates.
UB-VV111, another CD19-targeting in vivo CAR-T hematology asset from Umoja, is also in Phase I trials. Back in 2024, AbbVie signed a $1.4 billion biotech licensing deal to secure an option for future rights to UB-VV111, with an extension option for four additional in vivo candidates targeting specific antigens.
Addressing the growing target shortage, Pitchbook’s analyst suggests buyers may need to broaden their global search, as Chinese biotech enterprises are evolving into an indispensable global force.
Suzhou-based Starrymed completed a 300 million RMB (approximately 44 million USD) Series B financing last October, backed by investors including Lilly Asia Ventures. The company stated that part of the proceeds would support the advancement of its in vivo CAR-T pipeline.
As an RNA biotechnology firm, Starrymed has established two proprietary delivery platforms: tissue-specific LNPs and cell-selective LNPs. The latter technology conjugates ligands such as antibodies and proteins to LNPs to achieve precise targeting of specific cell subtypes, holding great promise for in vivo CAR-T applications. According to clinical trial information, its in vivo CAR-T candidate STR-P004 has entered investigator-initiated trial (IIT) stages for relapsed/refractory autoimmune diseases and CD19-positive relapsed/refractory B-cell non-Hodgkin lymphoma.
Recently, Honsun Biotech announced that its core pipeline candidate HN2301, with research findings titled In Vivo CD19 CAR-T Cell Therapy Induces Tissue B Cell Depletion in Systemic Lupus Erythematosus (SLE), has been selected for an oral presentation at the 29th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT).
According to official press releases, powered by its proprietary Engineered Cell-targeted LNP (EnC-LNP) platform, Honsun Biotech’s in vivo CAR-T pipeline is among the first globally to enter human clinical trials, making it the world’s first cell-targeted LNP drug tested in humans. Its landmark clinical findings have been published in the top-tier international journal The New England Journal of Medicine.
Chinese biotech players are increasingly active in the global in vivo CAR-T race. At the in vivo CAR-T Development In-depth Seminar hosted by Tongxieyi this March, an industry guest outlined the competitive landscape of China’s in vivo CAR-T sector. The track has split into two major technical camps: viral vector and non-viral vector.
Represented by Emostar and Fengxun Biotech, the viral vector camp focuses on optimizing lentiviral vectors to achieve precise in vivo cell transduction. The non-viral vector camp, led by Everest Medicines and CirCode Therapeutics, adopts LNPs to deliver mRNA or circular RNA, aiming to further reduce oncogenic risks and enable off-the-shelf accessibility.
Another speaker pointed out that lentiviral vectors boast more mature human clinical data and are widely recognized by multinational pharmaceutical companies, with strong focus on oncology indications. While LNP-based solutions still face uncertainties in solid tumor treatment, they present distinct advantages for autoimmune disease therapies.
3、Conclusion
Back in 2025, the publication of IIT research on EsoBiotec’s in vivo CAR-T candidate ESO-T01 ignited a global boom in the in vivo CAR-T field. Last month, a study in Nature Medicine systematically evaluated the safety, tolerability and preliminary efficacy of ESO-T01 in patients with relapsed/refractory multiple myeloma.
Combined analysis of the two key studies indicates that ESO-T01 failed to deliver superior efficacy, and accumulating data revealed substantial unresolved safety challenges.
The in vivo CAR-T sector now stands at a critical inflection point, marked by rapid technological differentiation, accelerating clinical data disclosure, and surging capital inflows. Which regulator will approve the world’s first in vivo CAR-T therapy? Which technology platform will gain official endorsement? Which indication will secure the first approval? Which company will submit the first BLA application?
Answers to these questions remain unclear. Yet one certainty remains: in vivo CAR-T will fundamentally reshape the entire cell therapy landscape.
For Chinese biotech enterprises, this global competition brings both unprecedented challenges and historic opportunities. Shifting from In China For China to In Global For Global, in vivo CAR-T may well serve as a fast track for Chinese innovators to achieve world-class biomedical breakthroughs.
References:
- After Lilly’s $7B Kelonia deal, are there any in vivo CAR-T biotechs left to buy?; Fierce Biotech
- Honsun Biotech’s In Vivo CAR-T Therapy Selected for ASGCT 2026 Oral Presentation, Ushering in a New Era for Autoimmune Disease Treatment; Honsun Biotech
- The "Chinese Legion" in the In Vivo CAR-T Arena; Tongxieyi
- The Rise of In Vivo CAR-T: A Full Review of Pipelines and Strategies Across 12 Enterprises; Hexincheng Biotech
- ESO-T01: No Clinical Surprises, with a Long Road Ahead; Tongxieyi
- Single Financing Over 300 Million RMB! 11 Deals in Total: Technology Competition and Clinical Breakthroughs Behind China’s In Vivo CAR-T Financing Boom; Yimaike
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