A less-than-six-year-old in vivo CAR-T startup is experiencing one highlight moment after another.

According to The Wall Street Journal, Eli Lilly is in advanced negotiations to acquire Kelonia Therapeutics in a deal valued at over $2 billion. Sources familiar with the matter indicate that if talks progress smoothly, an acquisition agreement could be announced as early as April 20 local time, with potential additional payments tied to Kelonia's achievement of certain milestones.

Kelonia possesses a lentiviral vector-based in vivo gene delivery technology platform called iGPS®. If the deal is finalized, this would mark Lilly's second major corporate acquisition in the in vivo CAR-T space this year, following its February acquisition of Orna Therapeutics, a leader in the LNP-RNA approach, for up to $2.4 billion in cash.

With this, Lilly has cumulatively invested over $4.4 billion to secure both mainstream in vivo CAR-T technology routes, establishing itself as the most significant player in the field.

TONACEA 01: Precision Engineering of Lentiviral Vectors

Founded in 2020 and headquartered in Cambridge, Massachusetts, Kelonia Therapeutics was established by Dr. Kevin Friedman, who brings over 20 years of experience in the cell and gene therapy field. As of 2026, the company has raised approximately $90 million.

Its core asset is the proprietary iGPS® (in vivo Gene Positioning System) platform—a lentiviral vector-based in vivo gene delivery technology platform that modifies lentiviruses to enhance in vivo gene transduction efficiency and engineers them to express targeting molecules for tissue specificity.

Unlike conventional lentiviral vectors, the core innovation of the iGPS® platform lies in its "active targeting" mechanism. The platform modifies lentiviral vectors by adding targeting molecules and fusogenic molecules.

Notably, this fusogenic protein is a modified vesicular stomatitis virus G glycoprotein (VSV-G), which cannot infect cells on its own. It is activated only after immune cells recognize the target antigen on the lentiviral vector, then mediating the delivery of the CAR gene into T cells.

This "conditionally triggered" design fundamentally reduces off-target risk. Furthermore, by simply swapping the envelope targeting molecule, the platform can be quickly adapted to different tissues or antigen targets, offering high versatility.

Kelonia is building a pipeline of in vivo gene drug candidates targeting a variety of indications based on the iGPS® platform. Its lead candidate is KLN-1010, an in vivo CAR-T cell therapy targeting BCMA.

KLN-1010 is currently in a Phase I clinical trial called inMMyCAR, designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of a single dose of KLN-1010 in up to 40 patients with multiple myeloma (MM). In January 2026, KLN-1010 received IND clearance from the FDA.

At the 2025 American Society of Hematology (ASH) Annual Meeting, Kelonia presented first-in-human data on KLN-1010 in patients with relapsed/refractory multiple myeloma (r/r MM) as a late-breaking oral presentation.

The abstract reported data from the first three (later updated to four) patients treated with KLN-1010. All patients achieved minimal residual disease (MRD) negativity by month one post-treatment, and the patient with the longest follow-up remained in complete remission (CR) at five months.

The study observed CAR-T cell expansion and persistence of memory CAR-T cells, all without the need for lymphodepleting chemotherapy, apheresis, or ex vivo cell manufacturing. Despite the absence of lymphodepletion, patients showed robust CAR-T cell expansion, with peak expansion around day 15 and CAR-positive cells accounting for up to 85% of T cells. Memory phenotype T cells persisted in the bone marrow and blood through month three.

On safety, no Grade 3 or higher cytokine release syndrome (CRS) occurred, no immune effector cell-associated neurotoxicity syndrome (ICANS) or delayed neurotoxicity was observed, cytopenias were significantly reduced compared to conventional CAR-T therapy, and no Grade 3 or higher hematologic toxicities occurred.

TONACEA 02: Giants Jockey for Position – Why Are MNCs Choosing It?

Notably, Lilly is not alone. Leveraging its proprietary iGPS® platform, Kelonia has previously entered into in vivo CAR-T collaborations with two other pharmaceutical giants: Astellas and Johnson & Johnson.

The collaboration with the former was reached in February 2024, combining Kelonia's iGPS® platform with the ACCEL™ platform of Astellas subsidiary Xyphos Biosciences, which features convertibleCAR immune cell technology.

Under the agreement, up to two target projects are contemplated. Kelonia will receive an upfront payment of $40 million for the first project. If Xyphos opts to pursue a second project, Kelonia will receive an additional $35 million.

Moreover, total potential milestone payments and contingencies approach $800 million. Kelonia will also receive funding for its R&D work on the collaboration projects and is eligible for tiered royalties on net sales, up to double-digit percentages.

The collaboration with Johnson & Johnson was quietly reached in November 2025, marking J&J's first foray into in vivo CAR-T and its first strategic bet on this technology route. The parties will utilize Kelonia's iGPS® platform to develop next-generation in vivo CAR-T cell therapies targeting J&J's areas of interest.

Shortly after the J&J collaboration, Kelonia disclosed clinical data for KLN-1010, providing important proof-of-concept for its technology platform.

A startup less than six years old attracting the attention of Astellas, J&J, and Lilly speaks volumes about the value of the iGPS® platform.

TONACEA 03: A Two-Pronged Strategy – Lilly's $4.4 Billion Chess Move

Regarding the technical path selection for in vivo CAR-T, the industry has long debated two mainstream directions: lentiviral vector-based in vivo delivery and LNP (lipid nanoparticle)-based non-viral delivery.

Lentiviral vectors benefit from the wealth of experience accumulated over more than a decade in the ex vivo CAR-T industry, offering inherent advantages in cell infection efficiency and stable, long-term CAR expression. They can integrate the CAR gene into the T cell genome, achieving stable expression that naturally aligns with the "long-lasting killing" needs of tumor therapy.

The LNP route offers advantages such as high transient expression safety, tunability, no risk of genomic integration, and simpler manufacturing processes. Although its non-integrating nature results in transient expression, its lack of genomic integration risk makes it ideal for autoimmune diseases—CAR proteins degrade naturally after clearing pathogenic B cells, avoiding long-term "immune overactivation" risks.

Lilly's strategic thinking is clearer than any other MNC: instead of choosing one route, it is securing both.

In February 2026, Lilly announced the acquisition of Orna Therapeutics for up to $2.4 billion in cash, doubling down on its in vivo cell therapy ambitions.

Orna's lead pipeline candidate, ORN-252, is a CD19-targeted in vivo CAR-T therapy, leveraging Orna's circular RNA platform and panCAR™ technology, intended for B cell-driven autoimmune diseases and ready for clinical initiation.

Preclinical data show that ORN-252 demonstrated more potent B cell depletion than rituximab in a lupus mouse model, significantly reducing dsDNA antibody titers. In non-human primate studies, a single dose achieved complete B cell depletion in peripheral blood and spleen, and post-treatment B cell reconstitution showed a decrease in switched memory phenotype and an increase in naïve B cell phenotype, suggesting potential "immune system reset."

Now, Lilly's agreement to acquire the lentiviral route player Kelonia for over $2 billion underscores its recognition of the long-term value of foundational technology platforms.

Strategically, this acquisition continues Lilly's diversification push. Fueled by substantial cash flow from tirzepatide and other GLP-1 drugs, the company has announced several major deals this year. Adding Kelonia to its portfolio would fill a CAR-T gap in the competitive hematological malignancy market, further reducing its reliance on any single blockbuster drug.

TONACEA 04: In Vivo CAR-T Enters the "Data Reading" Era

Since early 2025, in just over a year, the total transaction value in the in vivo CAR-T space has easily surpassed $10 billion, as multinational pharma giants have nearly bought out the top-tier overseas in vivo CAR-T innovative companies.

The logic behind the giants' rush is simple and brutal: in the early stages before technology routes have fully converged, secure the most promising platform companies through high-value acquisitions or collaborations, thereby avoiding lengthy early-stage R&D risks and stockpiling "nuclear options" for therapies that could disrupt the market in the future.

But no matter how compelling the platform story, ultimately, data speaks louder.

As more companies enter the IIT/Phase I stage, the pendulum of investment decisions is beginning to swing from "platform story" to "clinical data." Currently, at least eight in vivo CAR-T therapies have entered clinical trials globally, covering multiple indications including hematological malignancies, solid tumors, and autoimmune diseases.

Kelonia's ASH data—100% MRD negativity, no need for lymphodepleting chemotherapy, persistent memory cells—may have been the key to securing Lilly's "entry ticket."

In the next phase, competition in in vivo CAR-T will become even more fierce: only companies that deliver solid data will secure a place in the global race for next-generation cell technologies.

References:

1. Eli Lilly in advanced talks to acquire Kelonia Therapeutics for over $2 billion, WSJ says

2. Kelonia Therapeutics Announces Late-Breaking Oral Presentation of First-in-Human Data from in vivo BCMA CAR-T Therapy at the American Society of Hematology (ASH) 2025 Annual Meeting

3. BioValley, "The Direction of In Vivo CAR-T for Giants (Part 2): More Favor Toward Lentiviral Vectors"

4. In Vivo CAR-T: A Race of Money, Technology, and Time

5. In Vivo CAR-T: One Year After "Saturated Innovation"