How He Yuan Bio Conquered the CAR-T Development Challenge

(Source:JuventasSubscription Account）

Source: Zhongyuan Union Subscription Account

Recently, Juventas announced that Yuan Ruida has been approved by the National Medical Products Administration for the treatment of relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. This is the second drug approval Yuan Ruida has received in China following its 2023 approval for treating adult relapsed or refractory B-cell acute lymphoblastic leukemia, making it the only CAR-T cell therapy product in China currently covering two major hematological malignancy indications: leukemia and lymphoma.

Since its establishment in 2018, Juventas has been making waves in the blue ocean of cell and gene therapy. It not only successfully launched China's first self-developed CAR-T (Chimeric Antigen Receptor T-Cell Immunotherapy) drug, Yuan Ruida (Nageo Cell Injection), but also broke foreign monopolies with the lowest global commercialized CAR-T price tag of 999,000 yuan, bringing the revolutionary "one-time treatment, long-term benefits" therapy into reality.

"From the lab to the clinic, from China to the world, we have covered in 5 years what usually takes others 10, all thanks to the relentless determination to develop China-originated cell therapies!" Recently, inside the production base of Juventas, located in the Binhai High-Tech Zone, the company's founder and CEO, Lü Lulu, pointed to the equipment in the cleanroom workshop while sharing the story behind this China-based, self-innovated cell therapy company.

·The Benevolence of Doctors Ignites the Spark of Innovation

"The two 'bombshell announcements' in 2017 made me determined to step out from multinational pharmaceutical companies and devote myself to the research and development of China's self-innovated cell drugs," recalled Lü Lulu, whose resolve was firm as she spoke. With a background as a hematologist, she was all too aware of China’s passive position of ‘playing catch-up’ in the innovative drug field, having been involved in introducing Gleevec into China.

In 2017, the National Medical Products Administration (NMPA) explicitly included cell and gene therapies in the innovative drug approval system for the first time, opening a policy pathway for the industrialization of cell therapies; in December of the same year, Novartis’ world-first CAR-T product was approved for marketing in the United States, showcasing the immense potential of cell therapy to the world.

"On one side is the ‘reassurance’ of national policy, and on the other is the ‘beacon’ of global technology. More importantly, China already has a solid foundation in the field of cell research—so why can’t we develop our own original drugs?" Lü Lulu is determined to create China’s original cell therapy drugs, build an international industrial platform, and make this treatment accessible to patients worldwide.

In 2018, Juventas was officially established in Tianjin. "We chose Tianjin because it has a complete biopharmaceutical industry ecosystem that can provide us with full-chain support from research and development to production," said Lü Lulu. She introduced that since its establishment, the company has set its sights on a "high starting point." Not only did Juventas establish an in-depth collaboration with the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences (CAMS), but it also introduced the world's only exclusive "warhead" technology (the key structure in CAR-T cell therapy — the CAR construct) into its R&D efforts. Moreover, Juventas built a cross-disciplinary core team — members include experts from scientific research institutions as well as senior professionals from overseas pharmaceutical companies. Everyone gave up their previous stable jobs to gather in Tianjin for one shared dream: "to create a cell therapy drug made in China."

·Rigorous and pragmatic actions create "China Speed"

However, the cell therapy industry in 2018 was like an uncultivated wilderness — no mature processes, no readily available talent, and not even unified quality standards. Reflecting on the challenges faced during the early days of entrepreneurship, Lü Lulu still remembers vividly. At that time, there were only two CAR-T products approved globally, and no cell therapy products had yet been launched in China. Every step, from research and development to production, required navigating uncharted waters.

Process development was the first major hurdle. Unlike traditional chemical drugs, cell-based medicines have extremely high requirements for stability and safety in their production process. To overcome this challenge, Shi Lin, Juventas’ process leader at the time, led a small team of over 10 people in a "three-shift" mode, working around the clock in the lab to repeatedly test culture medium formulations, adjust cultivation temperatures, and modify carbon dioxide levels.

"At the most critical moment, we had to complete the technological transition from 'serum culture' to 'serum-free culture' within a year, which had no precedent worldwide," recalled Shi Lin. At that time, the National Medical Products Administration required that the quality of cell drugs produced in China "should not only be comparable to foreign standards but exceed them." To eliminate the infection risks posed by serum, the team had to develop serum-free culture technology.

During that period, the laboratory was often brightly lit throughout the night. "Since the cells don’t sleep, neither can we," said Shi Lin. Under the heaviest pressure, the young engineer couldn’t help but shed tears during a technical meeting, but after wiping away her tears, she continued to lead her team in conducting experiments. "Mr. Lü often says, 'Scientific rigor cannot tolerate any compromise,' and every piece of our data must stand up to scrutiny," Shi Lin remarked.

This persistence enabled Juventas to achieve a technological breakthrough within a year. Its serum-free cultured cell products not only met stability standards but also demonstrated efficacy and safety in clinical settings comparable to those of serum-cultured products.

With the spirit of tackling tough challenges, Juventas has created an impressive "China Speed" in the industry: founded in 2018, and receiving formal approval for the listing of Yuanruida in November 2023 — achieving a breakthrough from "0" to "1" in just five years, cutting the industry average cycle in half.

· "Don't let 'astronomically priced drugs' keep patients out of the door"”

"Twenty-eight days after the cell infusion, the leukemia cells in the bone marrow were eliminated, which is 'effective'; one year later, 90% of the patients are still healthy and alive, which is 'hope'." A set of data from Juventas is inspiring.

As China's first independently developed CAR-T product, Yuan Rui Da is mainly used to treat adult relapsed or refractory B-cell acute lymphoblastic leukemia. Its clinical application not only breaks foreign monopolies but also achieves breakthroughs in safety and accessibility.

"Our goal is to 'achieve success with every treatment.' " Introduced Dr. Lü Lulu, "To date, Juventas has treated over 500 patients, including more than 200 cases of adult leukemia, with an efficacy rate of 92.8% and a one-year survival rate exceeding 90%, far surpassing the effectiveness of traditional chemotherapy. More importantly, this therapy achieves 'one treatment, long-term benefits,' allowing the majority of patients to return to normal life without the need for bone marrow transplantation."

In terms of pricing, Juventas further demonstrates "China's responsibility." Currently, among the 14 approved CAR-T products globally, those from the United States are mostly priced between $360,000 and $470,000, while Juventas is priced at only 999,000 RMB, making it the world's only CAR-T product priced below one million RMB.

"We don't want 'astronomically priced drugs' to keep patients from accessing treatment," said Lü Lulu. Better news came as the company is actively promoting negotiations for medical insurance coverage: if successfully included in the national commercial insurance innovative drug list, combined with commercial insurance payments, patients’ out-of-pocket costs are expected to drop significantly.

· Bringing Chinese Original Drugs to the World

"The listing of Yuanruida is just our 'first car off the line,' and next, we need to make this car 'amphibious and flying globally.'" Standing at a new starting point for development, Lü Lulu has a clear plan for Juventas' future. Currently, the company has entered the "second phase" of its development. While consolidating the advantages of existing products, it is accelerating the advancement of a multi-product pipeline layout and international expansion.

In terms of indication expansion, Juventas has completed the registration and clinical trial application for pediatric indications. The efficacy rate for children aged 3 to 18 with relapsed or refractory B-cell acute lymphoblastic leukemia exceeds 90%, with a 5-year survival rate reaching 70%. Currently, approximately 100 pediatric patients have participated in clinical trials, showing significant effects. Additionally, the company is advancing into the field of autoimmune diseases, with multiple clinical studies initiated for systemic lupus erythematosus, autoimmune hemolytic anemia, and other related conditions.

Internationalization is an important strategy for Juventas. Currently, Yuanruida has been approved for marketing in Macao, China, and new drug marketing applications have been submitted in Hong Kong, China, and Saudi Arabia. Meanwhile, market expansion in countries such as Singapore and Japan is proceeding steadily.

"Cell therapy is at the forefront of a global medical revolution, and Chinese companies have the capability and responsibility to lead in this field," said Lü Lulu. Juventas aims to become a leading biopharmaceutical company driven by advanced cell and gene technologies during the 'third phase,' "but no matter how large we grow, our original mission remains unchanged — to make affordable, high-quality drugs for ordinary people and bring China-developed innovations to the world."

The growth story of Juventas is a microcosm of China's independent innovation in the biopharmaceutical industry. With the support of national policies and the perseverance of scientific researchers, an increasing number of Chinese original drug companies are breaking through "bottleneck" technologies. With a rigorous scientific attitude, affordable pricing strategies, and an open international perspective, they are bringing hope to patients worldwide while also...China MedicineContribute to the high-quality development of the industry.