On the 2nd floor of the Curocell(372320) production facility in Yuseong-gu, Daejeon, on the 24th.
Two biological safety cabinets (BSC), a cell separator, and culturing equipment were installed in five rooms separated by thick walls and glass windows. Each room is a sterile processing suite. This is where Korea's first CAR-T Therapy, "RIMQARTO," will be made.
◇ Preparing to launch RIMQARTO in the second half… "Expanding to solid tumors and in vivo"
RIMQARTO won Ministery of Food and Drug Safety approval in April as a third-line or later therapy for patients with diffuse large B-cell lymphoma (DLBCL). It passed the Cancer Disease Review Committee last month and is now headed into talks with the Drug Reimbursement Evaluation Committee and the National Health Insurance Service. Developer Curocell expects a listing with insurance coverage in the second half of this year at a price in the 300 million won range.
Preparations are also in full swing to supply more than 30 hospitals nationwide. Curocell CEO Kim Geon-su said, "We aim to begin dosing patients within the year and treat about 200 people next year," adding, "CAR-T is a therapy sought by patients who have no other options, but some patients find it hard to travel to Seoul, where large hospitals are concentrated. If CAR-T can be used in the provinces as well, it would be meaningful."
Curocell is also hurrying to expand RIMQARTO's indications. It will begin a phase 3 trial in Korea and Japan next year targeting second-line treatment for DLBCL. If the indication is broadened to second line, the number of eligible patients in Korea will increase by about 1,000 from roughly 600 a year.
Kim said, "We plan to submit an investigational new drug (IND) application within the year," and added, "We will expand indications to leukemia and autoimmune diseases and aim to grow domestic sales to the mid-100 billion won range within five years."
After RIMQARTO comes solid tumor CAR-T. Because solid tumors have dense tumor tissue and an immune-evasive environment, development is difficult, so CAR-T development has so far focused mainly on hematologic malignancies.
Curocell is developing solid tumor CAR-T targeting lung, colorectal, gastric, and prostate cancers. Some of these candidates are about to enter clinical trials. Joint research on lung and pancreatic cancer CAR-T with a Chinese partner is also underway.
A more distant goal is "CAR-T made outside the plant." Currently, CAR-T uses an ex vivo method, in which a patient's cells are taken out of the body, turned into a therapy, and then reinfused. In contrast, in vivo CAR-T produces CAR-T inside the patient's body, and there are no commercialized products yet.
◇ Different raw materials for every patient… why they built the largest plant in Asia
CAR-T is a therapy made for one person using that patient's own cells. The process is complex and quality control is difficult, making manufacturing capability a competitive edge in itself.
That is why Curocell began building its production facility in 2021, ahead of RIMQARTO's approval. Completed in 2023, the facility is about 10,000 square meters, the largest in Asia. It handles everything in one place, from production of viral vectors (carriers developed to deliver genetic material into cells) to CAR-T manufacturing, quality testing, and release.
The facility's current capacity is up to 700 patients a year. With commercialization of solid tumor CAR-T and in vivo CAR-T in mind, one floor has been left empty. The company says that using this space as well would expand capacity to up to 1,400 patients a year.
The build-out was arduous. Kim Hyeong-cheol, head of research and development (R&D) and director of the Research and Development Center, said, "At the time, Korea had almost no infrastructure for commercial CAR-T development," adding, "It was hard to find places producing viral vectors or clinical GMP facilities. There were also limits to securing patient blood for research purposes."
The CAR-T manufacturing process begins when the patient's blood arrives. T cells are extracted from the blood and activated, and a viral vector is used to modify the genes. The resulting CAR-T is cultured for five to nine days. When CAR-T has sufficiently expanded, unnecessary substances and debris from dead cells are removed and the concentration is adjusted for patient dosing.
An additive is then added to prevent cell damage and the product is frozen. After confirming for foreign matter and seal integrity, it is shipped to the hospital following quality tests.
Kim explained, "From a process development standpoint, activation was the hardest part," adding, "If activation is too strong, cells senesce, and if it's too weak, they don't grow well, so setting the proper standard was tricky."
In commercial production, differences in cell condition by patient are expected to be a variable. Patients who have undergone multiple rounds of anticancer therapy or are elderly may have fewer T cells, or lower cell viability and proliferation capacity. In such cases, the culture and finishing period can be longer.
Jeon Dong-hyeok, head of the Production Technology Center, said, "How quickly we identify abnormal signs in the initial cell condition and during culture will be key to reducing failures."
◇ To patients in 16 days… RIMQARTO competes not just on efficacy but on time
After launch, RIMQARTO will first compete with Novartis' "Kymriah." Kymriah is currently the only CAR-T in Korea covered by health insurance. Like RIMQARTO, it is approved as a third-line or later therapy.
Curocell touts treatment effect as its strength. In a Korean phase 2 trial, RIMQARTO posted a complete response (CR) rate of 67.1%. Kymriah's CR is around 40%.
Another competitive edge is "time." Curocell said it will take about 16 days from blood collection to shipment to the hospital. That is about half the roughly 30 days typical for overseas products.
Shorter supply time is directly tied to patient survival. CAR-T can be administered only if the patient's overall condition is maintained until the medicine is finished. The longer the supply period, the higher the chance of variables such as disease progression or complications.
Jeon said that the stages where blood is introduced into the manufacturing process and where quality tests are conducted are particularly important. "Even if the therapy is complete, if test results are delayed, patient dosing is delayed," he explained.
That is why Curocell was the first in Korea to obtain approval for a "rapid testing method." With the conventional approach, sterility testing takes 14 days, and mycoplasma and viral negativity tests take 28 days each, but with the rapid method, sterility testing takes seven days and the other two tests return results in one day.
For Korean patients, time can also be saved in the first stage. Unlike overseas CAR-T, RIMQARTO does not require sending blood across borders, shortening transport time. For the same reason, there is no need to freeze the blood.
◇ Selling plants, drugs, and technology… potential for overseas revenue next year
The experience of building a production facility opened the door to a new business for Curocell. The company is currently working with a Turkish corporation on a project to build a local CAR-T production facility and transfer the manufacturing process.
Kim said, "After RIMQARTO's approval, inquiries have increased from the Middle East, Russia, and South America," adding, "We are discussing business with four to five corporations." He predicted, "Because we are leveraging an approved product and manufacturing know-how, there will be no additional R&D expense burden, so we can generate high revenue."
Curocell also plans to pursue overseas business on two tracks: exporting finished RIMQARTO and platform technology transfer. It will target the Asian market first for finished goods sales, starting with Japan, and focus platform technology transfer on the United States and Europe.
Kim said, "We aim for a self-sustaining model that generates revenue from our own business and reinvests it into R&D," adding, "As sales could start next year from the Türkiye project, we will monitor conditions further before deciding on additional fundraising."