Huadao Bio Advances Full-Chain Localization to Slash CAR-T Therapy Costs by Nearly 80%

Mr. Yu Xuejun, formerly a hematologist at Changhai Hospital affiliated with the Second Military Medical University, engages in conversations with the patience characteristic of a seasoned clinician. Adept at using analogies and breaking down complex issues into manageable components, he embodies the military’s distinctive efficiency alongside a deep-seated sense of duty to his country and society. Within his clinical reasoning, the once-mysterious and exorbitantly priced CAR-T therapy holds the potential to become a standard clinical treatment, with the key lying in the ability to drive production costs down to their absolute minimum.

On Mr. Yu’s desk sits a photograph with a patient, a 19-year-old girl whose life he saved by administering CAR-T cell infusion after her relapse post-bone marrow transplantation (she has survived for four years to date). Throughout his medical career, Mr. Yu Xuejun has felt loneliness and helplessness, forced to watch over 400 of his hematology patients endure similar suffering and ultimately succumb to death. Traditional treatments such as chemotherapy and bone marrow transplantation can only prolong patients’ lives in the short term; more innovative technologies, such as cell therapy, are needed for effective treatment and cure.

Photo of Mr. Yu Xuejun on His Desk

As the most steadily developing branch of cell therapy, CAR-T therapy has gradually come into public view in recent years. With the successive approval of two CAR-T products in the United States, this technology has achieved a leap from scientific research to clinical application, but challenges in industrialization have subsequently emerged.

Mr. Yu Xuejun has developed a comprehensive solution for the industrialization of CAR-T therapy. Earlier this month, a VCBeat reporter visited HuaDao (Shanghai) Biopharmaceutical Co., Ltd., founded by Mr. Yu in Shanghai’s Zhangjiang Hi-Tech Park. The company’s independently developed automated CAR-T cell culture system has entered the simulation operation phase. Mr. Yu told VCBeat that it is precisely these machines, along with their supporting consumables and logistics infrastructure, that will make CAR-T therapy a more widely accessible treatment option.

HuaDao CAR-Tcell initiated CAR-T research in 2014 and formally launched investigator-initiated clinical trials in 2015. To date, it has completed treatment for over 70 cases and conducted long-term follow-up on many of these patients. Research results indicate that CAR-T therapy has indeed brought hope for survival to these patients. “Our goal is to make CAR-T therapy affordable for 80%–90% of patients.”

Within the CAR-T industry chain, Chinese companies’ patent capabilities are limited to upstream antibody structures and gene sequences. The complete reliance on imported key equipment, reagents, and consumables has resulted in a lack of independent pricing power, thereby limiting the potential for cost reduction.

On one hand, the high cost of cell preparation equipment itself, coupled with its exclusive occupancy during use, means that expanding the patient population is directly correlated with an increase in the number of equipment purchases. For instance, treating 10,000 patients annually would require nearly RMB 800 million just for the acquisition of cell culture equipment. On the other hand, each patient undergoing CAR-T therapy requires imported disposable consumables costing RMB 60,000 to 80,000, with overseas manufacturers monopolizing the pricing power for these consumables.

In this context, achieving full localization of the entire CAR-T industrialization process is undoubtedly the most direct solution. Mr. Yu Xuejun deconstructed the CAR-T industry chain and concluded that there is limited room for cost reduction in antibody screening and T-cell integration. Consequently, he focused on cell culture, transportation, and the development of operational management systems. After five years of exploration, HuaDao CAR-Tcell has established the capability for fully localized, end-to-end CAR-T industrialization across the entire supply chain. Its independently developed automated, closed-system CAR-T cell production equipment (including single-use consumables), personalized liquid nitrogen transport containers, and CAR-T cell storage equipment are poised for mass production at the Songjiang base. These advancements will reduce CAR-T cell production costs to 1/20–1/30 of those abroad and significantly accelerate the industrialization of domestic CAR-T cell products.

Another Bottleneck in the Industrialization of CAR-T Therapy for Solid Tumors. Clinically, CAR-T therapy can eradicate tumor cells in patients who are not surgical candidates, whose disease is uncontrolled by chemotherapy and radiotherapy, and whose tumor progression cannot be inhibited by interventional procedures. The industry has indeed initiated clinical trials enrolling patients with intermediate- to advanced-stage disease to verify the efficacy of CAR-T therapy; however, “these attempts are unlikely to succeed.”

Mr. Yu Xuejun explained that the reason lies in the fact that CAR-T therapy essentially induces a tumor lysis syndrome. Its applicability in hematologic malignancies is due to the relatively loose structure of lymphoid tissues, which prevents an excessively severe tumor lysis syndrome. In contrast, a solid tumor mass measuring 1 m³ contains more than 10¹⁰ tumor cells. Once immune cells are activated, they release large amounts of perforin, granzymes, and other cytokines, leading to tumor cell lysis. If the tumor lysis syndrome is too intense, the body cannot tolerate it, resulting in clinical contraindications that may accelerate patient death.

Moreover, although CAR-T therapy is feasible for solid tumors in the early stages, it does not offer significant advantages over other treatment modalities. “The reliable application of CAR-T in solid tumors should focus on preventing recurrence,” pointed out Mr. Yu Xuejun. This is a bold idea and a challenging path, but one that cannot be avoided. It is hoped that this butterfly effect will bring truly beneficial help to patients with solid tumors.

Beyond developing its own CAR-T therapies, Mr. Yu Xuejun aims to position HuaDao Bio as an industrialization platform that assists pure-play R&D enterprises and clinical immunotherapy experts across various medical specialties in accelerating the translation and commercialization of their innovations. He likens his work to building a highway: while only a few of his own “vehicles” travel on it, the infrastructure provides convenience for many more. The therapies emerging from the HuaDao Bio platform are designed to be affordable for Chinese patients, helping healthcare providers and patients reduce reliance on imported drugs.

Currently, the company is building a 15,000-square-meter full-industry-chain production base in Songjiang, Shanghai, establishing an ecological foundation for the entire industry chain that spans from upstream viral vector production to cell preparation and consumables manufacturing. Construction of the production base will officially commence in November, with delivery scheduled for June 2020 and mass production expected to begin by December of the same year.

In recent years, multiple companies in China have initiated Phase I clinical trials. However, since CAR-T therapies can be submitted for market approval without undergoing Phase III clinical trials, the manufacturing process must be finalized at the production facility during Phase II. The exclusive use of imported equipment throughout the process deprives companies of autonomous pricing power for their current CAR-T products. Consequently, these companies are hesitant to pursue market approval using existing industrialization solutions, thereby delaying the progression of clinical trials into Phase II.

“Making CAR-T a widely used drug is a long-term endeavor.” However, in Mr. Yu Xuejun’s view, patients receiving CAR-T therapy will benefit more than from any traditional treatment regimen. It has been disclosed that HuaDao CAR-Tcell has completed preclinical studies of CAR-T for leukemia treatment and will subsequently expand its pipeline to include gastrointestinal solid tumors.

HuaDao Bio’s cell therapy technology translation platform features a “Three-Shares, Two-Lows” model. The “Three-Shares” refer to the platform’s collaborative approach: 1. Shared production technology, with open access to both technology and the platform; 2. Shared production costs; and 3. Shared product revenues, distributed proportionally. The “Two-Lows” denote the platform’s development goals: achieving low-cost R&D and low-cost intelligent manufacturing.

Mr. Yu Xuejun emphasized that HuaDao Bio promises that the market price of CAR-T drugs manufactured on its CDMO platform will be independently priced and affordable for both the public and medical insurance schemes. “We aim to leverage this platform to relentlessly control R&D and production costs, accelerate the industrialization of CAR-T therapies in hospitals and research institutions, and deliver more affordable CAR-T cell therapies to the Chinese public more quickly and effectively.”