IIT (Investigator Initiated Trial), also known as “non-registrial clinical research,” is different from the New Drug Clinical Trial (IND) led by pharmaceutical companies. IIT is a research protocol initiated by clinical investigators with clinical needs at its core.

The orderly exploration of IIT in China is supported and defined by a gradually improved regulatory framework with clear goals.

The “Measures for the Administration of Investigator-Initiated Clinical Research Conducted by Medical and Health Institutions,” officially issued in 2024, has given IIT a “backbone” — clarifying that medical and health institutions are the primary responsible entities, requiring pre-review of both “scientificity and ethics,” and regulating the management of high-risk research.

However, the above-mentioned measures mainly focus on post-marketing IIT research. For example, in the oncology field, IIT research can be used to explore dose optimization, sequential treatment regimens, combination treatment regimens, etc., to help optimize clinical treatment.

For more cutting-edge cell and gene therapy technologies, IIT research is not limited to post-marketing. The “Measures for the Administration of Stem Cell Clinical Research (Trial)” issued in 2015 and the “Guidelines for Somatic Cell Clinical Research (Trial)” in 2023 provide compliance support for early IIT research in this field (clinical research stage or even earlier discovery stage).

“Overseas peers do not fully understand the composition of China’s high efficiency and simply equate high efficiency with IIT. There is no Chinese-style IIT in the United States; the U.S. only has individual approval for compassionate use in single cases. China’s IIT is similar to group approval for compassionate use,” Zhang Dan, co-founder and co-chairman of Puxin Biotechnology, pointed out to Tongxieyi.

On this basis, in the United States, whether it is compassionate use or non-compassionate normal use, all human drug use pathways must ultimately converge to a single FDA approval window; while in China, IIT and IND are two parallel access tracks under the National Health Commission and the National Medical Products Administration respectively.

Currently, the latest breakthrough of this framework lies in the fact that the new regulations provide a potential “value closed loop” for cutting-edge technologies.

According to the “Regulations on the Administration of Clinical Research and Clinical Transformation and Application of New Biomedical Technologies” (Decree No. 818), officially released on October 10, 2025, high-quality IIT results can be transformed into chargeable clinical diagnosis and treatment projects in the medical institutions where the research was completed after approval.

This means that a successful exploratory clinical study may itself open up the path from scientific verification to initial commercial application, which is also an innovation worldwide.

IIT’s unique model has played a key role in promoting China to become a global competitive force in the field of cell and gene therapy.

Gao Chenyan, a senior scientist at Changping Laboratory, once pointed out: early IIT research can not only empower innovation but also conduct early human trials and proof-of-concept, helping to quickly determine suitable targets, verify product design, and timely improve problems (such as sequencing research, product design changes, etc.), providing support for subsequent druggability research.

This setting, based on clinical value, directly responds to the “pain points” of CGT research.

“CGT therapies often face patients with advanced, relapsed, refractory diseases for which existing treatments have failed,” Guo Zhigang, professor at Nanjing Normal University and chief scientist of Miracle Biotechnology, pointed out to Tongxieyi. “If there is a new possible treatment, from the ultimate goal of human health and well-being, enabling patients to benefit as soon as possible is undoubtedly significant.”

At the same time, the flexibility of IIT protocols has greatly reduced the “trial-and-error cost” of corporate research.

CGT technology iterates rapidly, and core elements such as targets and vectors often need repeated verification, while IND protocols are difficult to modify once determined. Most IITs are small-sample studies, which can not only verify technical feasibility at a low cost but also quickly screen out potential R&D directions, avoiding pharmaceutical companies from “wasting resources” on ineffective technical routes.

An intuitive metaphor is: the conventional new drug R&D process is like building a cross-sea bridge, which can only start construction after all drawings, materials, and construction permits are in place; while IIT is more like erecting an emergency floating bridge, allowing the most critical people and vehicles to pass first, then iterating and reinforcing it.

Guo Zhigang also mentioned: “For many drugs, only safety can be observed in Phase I clinical trials, and efficacy is often not seen until Phase II. However, IIT protocols are relatively flexible, and many IIT studies can observe both safety and efficacy signals simultaneously.”

This is essentially a forward-looking risk control — only when the concept is initially verified in IIT can the subsequent large-scale investment in registrial clinical trials be more assured.

On a further dimension, IIT has greatly shortened the cycle from laboratory molecules to clinical verification.

“After a product completes molecular development, the speed of reaching the clinic through the IIT path is greatly accelerated, making the efficiency of the entire molecular iteration and optimization multiply,” Guo Zhigang added.

In recent years, two model cases have demonstrated in a highly convincing way how IIT data has evolved from laboratory charts to “hard currency” that shakes the global industrial pattern, and also intuitively confirmed the commercial value of IIT.

One of them is the highly watched in vivo CAR-T company EsoBiotec, a Belgian company founded in 2020 with initial funding of only 20 million euros. Earlier in 2025, the company was still a micro-enterprise with only 12 employees.

Despite limited resources, EsoBiotec successfully achieved what its better-funded peers failed to do: it became the first company to report clinical data on in vivo CAR-T therapy.

This was achieved under China’s IIT innovation mechanism: EsoBiotec cooperated with Chinese doctors and announced the launch of an IIT (Investigator Initiated Trial) of its in vivo CAR-T product ESO-T01 in China in December 2024; one month later, early remission data of a single patient was released, with cancer cells cleared in 28 days.

On March 17, 2025, AstraZeneca announced that it would acquire EsoBiotec for 1 billion US dollars, with an upfront payment of 425 million US dollars.

Subsequently, in July 2025, Esobiotec published IIT clinical research data of ESO-T01 in treating 4 multiple myeloma patients in “The Lancet.” The ORR of the 4 patients reached 100%, 2 patients achieved stringent Complete Remission (sCR), and 2 patients achieved Partial Remission (PR), becoming important breakthrough data in the early stage of in vivo CAR-T.

These news items form a timeline, and thus, the “legend” of EsoBiotec has been circulating in the industry: 12 employees, 1 case of early IIT data, and in less than 4 months, directly drove a 1 billion US dollar acquisition by a multinational corporation.

“China’s regulatory flexibility saved us at least two years,” JP Later, CEO of EsoBiotec, also admitted in a report by Endpoints.

Another longer-lasting and more far-reaching case comes from a Chinese local enterprise — Legend Biotech.

In 2017, Legend Biotech announced IIT research data on a CAR-T therapy for multiple myeloma (later known as Carvykti), with amazing results.

These early data immediately generated strong appeal. In the same year, pharmaceutical giant Johnson & Johnson reached a global cooperation with Legend Biotech, with an upfront payment of up to 350 million US dollars.

The two parties agreed that in the global market, Legend Biotech and Johnson & Johnson would share costs and profits in a 50:50 ratio, and Johnson & Johnson would be responsible for price approval and market access — this transaction can be regarded as one of the pioneering BD deals for Chinese innovative drugs going global.

Since then, Carvykti was approved for marketing by the U.S. FDA in 2022 for the treatment of multiple myeloma patients who have received four or more lines of treatment, and its sales have been rising all the way. By 2025, Carvykti has become a new “blockbuster drug” with a global sales volume of 1.887 billion US dollars, and Legend Biotech “enjoys” the share.

These two cases are frequently mentioned because they truly provide the imagination of IIT implementation and offer a textbook explanation for “how IIT data can be converted into huge commercial value.”

Benefiting from the unique advantages demonstrated by IIT and the value implementation cases it has spawned, some U.S. biotechnology investors have called on the FDA to learn from China’s model and allow decentralized approval mechanisms for first-in-human trials.

At the same time, more pharmaceutical companies have chosen to take direct action: Umoja Biopharma, a star company in in vivo CAR-T, selected China for its first clinical trial; Kite, a subsidiary of Gilead, also reached a strategic cooperation with Puruijin Biotechnology, which is EsoBiotec’s partner in China.

During this year’s JPM Conference, IIT simply became a “pet phrase” among foreign companies. A participant mentioned: “Whether they asked me, the Chinese people around me, or even some panels, they would ask: is it particularly easy to do IIT in China? Can foreign companies do it? Do you need GMP for IIT? Is the data reliable?”

This series of questions also reflects, to a certain extent, the “stereotypes” of European and American peers about China’s IIT.

In the narrative of some overseas observers, the unique advantages of IIT have been simplified and even alienated into the triple labels of “cheap, quick, quiet,” and further misinterpreted as meaning “loose regulation” and “semi-compliant” production (the so-called “GMP-like” or “half to GMP”).

In fact, China’s IIT has its own rigorous and multi-level compliance management system. An IIT project needs to pass a series of strict checkpoints from initiation to completion.

In an interview, an expert with dual clinical and industrial backgrounds explained the process and rigid standards of IIT from a practical perspective, combining regulatory requirements and his own experience.

First of all, it is by no means “open to all.” The project must be initiated by a senior investigator from a Grade A tertiary hospital, and the hospital itself must have a sound clinical research management structure.

The sponsor must provide a complete set of data including product process, quality control, and necessary preclinical safety and efficacy data to initially demonstrate that the risks of human trials are controllable.

IIT Project Approval and Implementation Process Announced by the Clinical Research Center of a Hospital

Subsequently, there is a rigorous multi-level review: scientific review by the hospital’s academic committee, ethical review by the ethics committee, and filing with the provincial and even national health administrative departments. The research can only be initiated after obtaining the final filing number.

Throughout the research process, the protection of patients’ rights and interests is placed at the top priority. Signing a detailed informed consent form is a prerequisite. At the same time, purchasing clinical trial insurance for patients participating in the research has become a rigid requirement of many ethics committees to deal with possible unknown risks.

In terms of research execution, although it is not necessarily mandatory to be equipped with a large-scale CRO team for full supervision like registrial clinical trials, standardized data recording, regular safety monitoring, and formal statistical analysis after the end of the research are all essential links.

In short, the remarkable “speed” of IIT does not stem from compromises in scientific or ethical standards, but from the optimization of regulatory paths.

It places part of the approval authority for early exploration in medical institutions that are closer to clinical practice and have shorter decision-making chains, thereby bypassing the long and complex preliminary links of IND approval and achieving “rapid initiation” under strict ethical and scientific supervision.

The enthusiasm of the global pharmaceutical industry for China’s IIT is far more than just looking for a “shortcut.” What they really care about is the possibility of systematically optimizing risks and returns through institutional design in the highly uncertain cutting-edge field, thereby reshaping the early R&D paradigm.

China’s exploration of IIT, with “dual-track regulation” as the core, “clinical value” as the focus, and “high efficiency and flexibility” as the characteristics, not only provides a path for rapid trial-and-error and iterative optimization of cutting-edge technologies such as CGT but also builds a bridge for the commercial transformation of innovative achievements — the counterattack of EsoBiotec and the rise of Legend Biotech are vivid evidence of the value of this model.

Of course, the maturity of this “Chinese path” is still in progress: the balance of research quality, the sustainability of funding sources, the smoothness of data transformation, and the further improvement of international recognition are still issues that need to be addressed.

But it is undeniable that this innovative path derived from China’s clinical practice has moved from “China-specific” to “global attention,” and from “being examined” to “being embraced” and “being learned from.”