Efforts to replace the high-priced chimeric antigen receptor T-cell (CAR-T, Kymriah) therapy, which costs billions of won, with a single injection are gaining momentum.
This is because in vivo CAR-T, which creates therapeutic cells directly inside the body instead of the existing method of culturing patient cells outside the body, is emerging as a next-generation cell therapy. Global pharmaceutical companies are continuing to invest, as it can significantly reduce time and expense.
On the 9th (local time), Eli Lilly and Company said it would acquire U.S. biotech Orna Therapeutics for up to $2.4 billion (3.5 trillion won).
Orna's core pipeline is an in vivo CAR-T–based therapy under development with B-cell autoimmune diseases as the main indication. With this acquisition, Lilly aims to expand its existing immune disease portfolio, centered on antibody and small-molecule therapies, into the next-generation cell therapy space.
CAR-T cell therapies are called the dream anticancer drugs because they can selectively attack cancer cells and minimize damage to normal cells. They have also drawn attention as a one-shot therapy because, once administered, they proliferate in the body and continue to eliminate cancer cells.
To date, a total of seven CAR-T therapies, including Novartis' Kymriah and Gilead Sciences' Yescarta, have received approval from the U.S. Food and Drug Administration (FDA) and are used to treat blood cancers.
However, existing CAR-T therapies require a complex manufacturing process of culturing and manipulating a patient's cells outside the body, taking weeks to reach treatment, and the expense has reached hundreds of millions of won.
In vivo CAR-T skips these steps and induces CAR-T cell generation directly in the body, and, if commercialized, is expected to greatly improve access to treatment for chronic diseases such as autoimmune diseases and cancer.
Recently, clinical results showing the potential of in vivo CAR-T have also emerged. Belgium's EsoBiotech said last July that with a single administration, it confirmed complete remission—meaning a cure—in two of four multiple myeloma patients, and the remaining patients showed a partial remission response in which some cancer cells disappeared.
This has accelerated the race among global pharmaceutical companies to secure technology. The United Kingdom's AstraZeneca acquired EsoBiotech for $1 billion (about 1.45 trillion won), and U.S. firm Bristol-Myers Squibb (BMS) also acquired Orbital, which is developing in vivo CAR-T therapies, for $1.5 billion (about 2.185 trillion won) in Oct. last year.
AbbVie and Gilead have also jumped into related technology development through mergers and acquisitions (M&A). The industry believes that more than 100 in vivo CAR-T pipelines are in development worldwide.
Amid this trend, domestic corporations are also moving to develop in vivo CAR-T. AbClon, which is developing the CAR-T cell therapy Nespecell (AT101), is a prime example.
AbClon said on the 5th that it began developing an in vivo CAR-T platform. The company is conducting a phase 2 clinical trial of the CAR-T therapy candidate AT101 (Nespecell) for relapsed or refractory diffuse large B-cell lymphoma, and said it confirmed positive therapeutic effects in the process. Based on this, it plans to expand its research scope to a platform that implements CAR-T in the body.
AbClon is also developing a switchable CAR-T platform, zCAR-T (AT501), targeting solid tumors. The idea is to use switch molecules to control the activity of CAR-T cells, thereby improving toxicity and tumor target heterogeneity issues. The company is also working to secure delivery vector technology suitable for mass production through joint research with domestic and overseas corporations, including a Swedish venture company.
A company official said it would work to realize the ultimate goal of "same-day CAR-T injection at the hospital."
The key to commercializing in vivo CAR-T is how efficiently a small amount of genetic information can be delivered to immune cells.
In this regard, Surginex is developing a lipid nanoparticle (LNP) platform that selectively delivers genetic information to the spleen, which is responsible for the body's immunity. The industry believes that the completeness of delivery vector technology will be the key factor determining the competitiveness of in vivo CAR-T.