Over the past decade, China's life sciences and health technology sector has seen no shortage of highlight moments: financing rounds, IPO bell-ringings, global expansion. Behind these shining moments, beyond timing and favorable conditions, there is a group of relentless founders who genuinely embrace the spotlight while also bearing hidden lows, difficult choices, and trade-offs.

 

Wei Cao is one of them.

 

As a serial entrepreneur, he was Co-founder, former President and CEO of CBMG (now AbelZela), as well as Founder, Chairman and CEO of Gracell Biotechnologies. In the fifteen-year history of China's biopharmaceutical industry, few have rung the Nasdaq bell twice and successfully achieved exits both times.

 

Looking back on his entrepreneurial journey, Cao jokes that he has "stepped into every possible pitfall": from the policy ambiguity of the early days to the Nasdaq listing highlight, securing financing just before the industry downturn, completing strategic layouts just before regulatory tightening, and finally concluding with a beautiful acquisition—he has lived through the full lifecycle of China's first-generation biotech.

 

Even more surprising, two years after the acquisition of Gracell, Cao published a book, Decoding Biotech Entrepreneurship, distilling his fifteen years of entrepreneurial experience.

 

In a business world that pursues efficient returns, writing a book might be one of the most disproportionate investments of time and energy relative to output. But what Cao values is the spillover value of knowledge and experience: "If it helps even two or three companies avoid detours, that is an indirect contribution."

 

This is a methodological manual for entrepreneurs. As written on the back cover: "This book attempts to answer not just 'how to start a biopharmaceutical company,' but how to redefine the value of life within the three-dimensional coordinates of science, business, and humanity."

 

Yu Dechao, Founder, Chairman and CEO of Innovent Biologics, wrote in the foreword: "Dr. Cao uses his personal experience as a pen to frankly lay out the truths of entrepreneurship in innovative biopharma... These experiences are too precious—if I had been able to read Decoding Biotech Entrepreneurship when I founded Innovent, I might have avoided many detours and built the company on a firmer foundation."

 

Cao often says, "A founder CEO is very lonely." But at this moment, one entrepreneur resonates with another—perhaps loneliness does not directly connect, but it can echo.

 

 

TONACEA 01: The Founder's Instinct and Judgment

 

The essential characteristics of entrepreneurial opportunities include timing, conditions, and possibilities. Clearly, the broader social and industry environment is the foundational condition for entrepreneurial opportunities, while other conditions constitute the necessary factors entrepreneurs must consider, including the entrepreneur's own qualifications, team, policy and economic conditions, capital markets, and the technology and products possessed by the venture.
— Decoding Biotech Entrepreneurship, Chapter 1

 

"In the beginning, the CEO of an innovative biopharmaceutical company must be a biologist," Cao states directly.

 

He believes that many smart people—those with finance or engineering backgrounds—can succeed in management, but that applies to mature companies, especially late-stage commercial-focused ones. At that stage, a technical CEO may actually need to be replaced, because their perspective is often limited to technical details, preventing them from making holistic judgments from a commercial return perspective.

 

But early-stage is completely different. The goal in the startup phase is technological innovation, which is fraught with the possibility of failure. When a product or technology is iterated every two to three years, the CEO must make precise judgments. The basis for those judgments is not hearsay but a solid foundation in biology, pharmacology, and immunology. Otherwise, it is easy to slide into me-too development.

 

Cao himself is a typical technology-focused founder. Born in 1958, he lived through the Great Famine and the "Down to the Countryside" movement. He earned his medical degree from Fudan University School of Medicine, then traveled to the U.S. to pursue a Ph.D. in pharmacology at Eastern Virginia Medical School, followed by postdoctoral research at Harvard Medical School and Stanford School of Medicine. He then moved into industry, holding senior positions at Chiron (later acquired by Novartis and Bayer) and Affymetrix (now part of Thermo Fisher Scientific).

 

At the end of 2010, Cao co-founded Cellular Biomedicine Group (CBMG) (now renamed AbelZela) and served as its CEO. CBMG chose the cell therapy path from the beginning: its main pipeline was autologous adipose-derived and umbilical cord-derived mesenchymal stem cells for the treatment of knee osteoarthritis (KOA). Before its IPO, CBMG also began developing CAR-T therapies.

 

After three and a half years, on June 18, 2014, CBMG became the first Chinese cell therapy R&D company to list on Nasdaq. Two years later, Cao stepped down as CEO.

 

Reflecting on the history of China's biopharmaceutical development from 2010 to 2016, Cao says, "This period was the 'foundation-laying era' for China's transformation from generics to innovation. Policy support was continuously strengthening, the capital environment was gradually improving, and a foundational ecosystem for innovative drug R&D, antibody platforms, industrial parks, and approval reforms was initially established."

 

Through this entrepreneurial journey, Cao gained valuable and replicable experience in all aspects: company creation, R&D, financing, going public, and then post-IPO quarterly reporting and investor relations management.

 

More importantly, his experience at CBMG also gave him a clear view of the immense challenges and boundless opportunities in the CAR-T field. In 2017, after witnessing the first CAR-T therapy receive marketing approval, he couldn't settle for comfort—he decided to start from scratch and go through the 0-to-1 process again.

 

In May 2017, Gracell Biotechnologies was founded, entering the CAR-T field with a commitment to developing highly differentiated products and addressing major industry problems.

 

At that time, the astonishing efficacy of CAR-T in late-line hematologic malignancies had ignited industry-wide enthusiasm, but problems were equally prominent. The production process for classic autologous CAR-T products is personalized, cumbersome, and costly. Patient accessibility to cell therapies was vastly different from conventional drugs.

 

Cao's judgment was that CAR-T therapy for solid tumors would need to improve its cost-effectiveness to compensate for its high cost and low accessibility. He did the math in his head: if CAR-T couldn't become more cost-effective, even the best technology might remain a laboratory decoration.

 

The key question had to be asked: How can we improve patient access to drugs?

 

TONACEA 02: Develop Products Patients Need

 

Product pipelines must demonstrate industry-leading safety and efficacy, combined with robust manufacturing technology and cost flexibility, to collectively deliver high cost-effectiveness. A drug with vitality should meet one key word: high cost-effectiveness.
— Decoding Biotech Entrepreneurship, Chapter 4

 

In the beginning, Gracell focused on CAR-T for solid tumors.

 

Cao believed that the design goals for advanced CAR-T therapies for solid tumors should include: high ability to migrate into tumor tissue, ability to overcome the tumor microenvironment (TME), effective expansion and killing of tumor cells, and furthermore, CAR-T cells must survive in vivo for more than several months to have the opportunity to ablate tumor tissue.

 

Recalling that stage, Cao said, "We were the first to knock out PD-1 on CAR-T to relieve PD-L1 suppression. We were very excited about the idea. But when we tested it on patients, clinical indicators did improve, but without significant benefit."

 

He calmed himself down and kept asking the same question: For such an expensive, complex product that only brings modest improvement in biomarkers, without even long-term OS data yet—why would patients pay for it?

 

Cao told a heavy and heartbreaking story: "There was a college student whose doctor said he was unwilling to enroll in the trial. We looked into it—it turned out the barrier was hospitalization fees, lab tests, and other costs, totaling less than RMB 20,000. He didn't want to burden his family further, so he left." Cao paused. "A young college student with late-stage relapsed leukemia, who had a chance to survive, ultimately gave up his life."

 

He realized that if even RMB 20,000 in hospitalization fees could be the difference between life and death, then a product costing over a million yet only providing "improved biomarkers" would, even if approved, help very few patients.

 

In the early days, resources and capital were limited. "You have to gauge whether you have enough oxygen to swim across the Yangtze River." Based on this realistic assessment of patient needs, Gracell abandoned this development direction and turned to dual-targeting CAR-T, while simultaneously advancing the FasTCAR technology platform in parallel.

 

The core breakthrough of the FasTCAR platform was reducing production time from the traditional two weeks to next-day (22-36 hours). It employed a concurrent activation-transduction mechanism, allowing T cells to be activated while being genetically modified, eliminating the need for prolonged ex vivo expansion.

 

The results were: significantly lower per-batch costs, with cleanroom maintenance and facility equipment depreciation costs reduced by more than 70%; younger cell phenotypes with 10 to 30-fold improved expansion capacity; clinical trials demonstrated higher efficacy and excellent safety. Meanwhile, patient waiting times were greatly shortened, the opportunity for disease progression was reduced, and the need for bridging therapy decreased. The reduction in manufacturing costs ultimately translated into improved accessibility of CAR-T therapy.

 

"The dual-targeting data was solid, and FasTCAR solved many older manufacturing problems. Combining the two gave us GC012F," Cao recalled about the birth of Gracell's core product.

 

GC012F is a BCMA/CD19 dual-targeting CAR-T therapy, covering multiple hematologic malignancies and autoimmune diseases. By the time of the acquisition, its most advanced indication, relapsed/refractory multiple myeloma (RRMM), was already in Phase Ib/II clinical trials in the U.S.

 

This is the cruelest yet most fascinating aspect of entrepreneurship: at every fork in the road, you have to make a choice, and no one tells you which path is right. You can be ignited by an idea and stay up all night; you can also personally extinguish a direction you once deeply believed in, simply because the data "wasn't good enough."

 

Cao asked rhetorically, "Why do some companies gradually fade away? Why do others get smoother and start to be noticed? The answer is simple: it's not luck, but that at those critical junctures, someone made the right choice."

 

TONACEA 03: Downturns Are the Norm in Entrepreneurship

 

In the process of entrepreneurship and growth in the biopharmaceutical field, technological innovation is certainly the cornerstone, but capital management is the lifeline that enables a company to continuously advance R&D, cross critical thresholds, and ultimately achieve commercialization. For early-stage pre-revenue companies in particular, how to scientifically manage funds, effectively advance financing, and formulate appropriate IPO strategies not only determines whether the company can survive the "valley of death" but also affects its image and long-term development potential in the capital markets.
— Decoding Biotech Entrepreneurship, Chapter 6

 

After its founding, Gracell completed four rounds of financing in four years, with investors including 6 Dimensions Capital, Lilly Asia Ventures, Temasek, and OrbiMed.

 

In 2021, Gracell successfully listed on Nasdaq. The offering price was US$19 per ADS, and on its first day of trading, the stock rose more than 50% intraday, closing at US$25.06, up 31.89% from the offering price, giving the company a market capitalization of US$1.64 billion at one point.

 

This was the highlight moment in the public eye. But no company can stay at its peak forever; most of the time, it moves forward amid fluctuations. Behind many highlights lie hidden troughs that few know about. Cao admitted, "During the founding of both companies, I faced difficulties and low points."

 

During the CBMG era, social venture capital and state support were scarce. Although some biopharmaceutical R&D companies had been established, funding sources remained limited, with a significant portion coming from entrepreneurs and executives in other industries—real estate, semiconductors, electronics.

 

"Moreover, the pace of fundraising back then was far from as comfortable as it is today. Now people start fundraising before they are completely out of money. Back then, we waited until we were out of money to start raising. During the toughest times, our executives voluntarily took three months without pay."

 

Gracell went through something similar. In 2018, Gracell decided to initiate construction of its GMP manufacturing facility in Suzhou BioBay. By the end of the second year or beginning of the third year, with R&D centers established and GMP facilities under construction on two fronts, while simultaneously initiating IITs, funding suddenly became insufficient. "Actually, several leading investment institutions had shown interest, but until contracts are signed, nothing is certain. That pressure is very real."

 

Even more agonizing than being short of money was the persistent downward slide of the stock price after going public.

 

Gracell's IPO coincided with the peak of the global biotech bubble. What followed was a three-year-long capital winter. Starting in the second half of 2021, Fed rate hikes, geopolitical tensions, and the bursting of the industry bubble led to a collapse in the biotech sector.

 

Adding to that, after the IPO, to build a deeper moat, Gracell rapidly expanded its technology platforms: from FasTCAR and TruUCAR (universal CAR-T) before the IPO to SMART CAR-T, enhanced CAR-T for solid tumors, adding two new technology platforms, doubling the size of its R&D and technical teams.

 

The footprint kept expanding, but the chill in the capital markets grew ever colder. Gracell entered a dark period.

 

Despite strong clinical data, the stock price continued to decline. "No matter how positive the clinical data we released, the stock price wouldn't move—or would even fall. The company's fundamentals were completely disconnected from the market."

 

Cao said, the capital markets call this cycle a "cycle," implying recurrence, but for entrepreneurs, entering a downward cycle is a visceral pain. "The management team put their own money into buying back shares, but it was like throwing stones into the ocean—no reaction at all. The money was gone, and the pressure only increased."

 

To survive, Gracell decisively adopted a "cut losses to survive" strategy, suspending or scaling back investment in most pipelines, closing its R&D center in the U.S., and concentrating resources on the FasTCAR-T pipeline, especially the GC012F program.

 

The target set by the company was to commercialize GC012F for its first indication in 3-4 years. At the same time, leveraging the marginal effects of clinical study results from treating multiple indications with the same product (including early-stage refractory multiple myeloma and advanced lymphoma, both of which had published impressive data), the team confidently entered the autoimmune disease field.

 

This strategic shift became a turning point for subsequent major events at Gracell. Thereafter, the company successfully completed technology transfer to Lonza, an internationally renowned CMO, and received IND approvals from the FDA for two indications of its core product, GC012F.

 

TONACEA 04: The Philosophy of Going Global and BD

 

In the next five years, business development capability will remain a key element in the development of Chinese biopharmaceutical enterprises. When formulating business development strategies, companies need to comprehensively consider market conditions, their own strength, R&D stage, and many other factors. Companies with differentiated technology platforms and international teams are more likely to attract the interest of multinational pharmaceutical companies.
— Decoding Biotech Entrepreneurship, Chapter 7

 

During Gracell's development, Cao clearly felt the changes in the landscape and ecosystem of the biopharmaceutical industry.

 

On one hand, although China's biopharmaceutical industry started late, it has entered a leapfrog development stage over the past decade—progressing from following, to running alongside, and now leading in some areas, gradually gaining the attention of the global market. Take the number of clinical trials as an example: in 2024, the number of clinical trials conducted in China exceeded that of the United States.

 

On the other hand, the financing climate for China's innovative drugs in the primary market reached an unprecedented peak in 2021, after which it turned sharply downward. The tightening of funding placed unprecedented pressure on companies, making it difficult for many to maintain daily operations and advance R&D.

 

Under such circumstances, "going global" became a key pathway for R&D-driven biopharmaceutical companies to generate cash flow.

 

As early as 2020, the third year of the company's founding, the Gracell team began participating in major academic conferences and global BD meetings (such as the JPM Annual Meeting), attempting to reach out to MNCs that had already initiated CAR-T product development. However, after communication, they found that the real interest of these MNCs was to understand Gracell's technology or products as competitors.

 

They did not give up. Cao hired an experienced CBO, whose first task was to map out potential buyers' interest profiles: which MNCs did not yet have a leading technology platform in the CAR-T field, and which might be interested in hematologic malignancies. They identified targets and reached out to the BD teams of MNCs through various channels.

 

The real turning point came after the JPM conference in January 2023—the Gracell team met with representatives of AstraZeneca's Oncology Business Unit from China and shared the technical advantages of FasTCAR's "next-day manufacturing" and the clinical data of their dual-targeting CAR-T.

 

In February, representatives from AZ's headquarters BD team based in China, along with BD members from headquarters, visited Gracell's Shanghai headquarters. The other side showed strong interest.

 

Initially, it looked like a conventional license-out negotiation. However, during due diligence and negotiations, AZ's attitude underwent a subtle shift.

 

"Over about six months, we had continuous exchanges, covering all aspects of the technology and product. Unexpectedly, we received a verbal proposal from AZ's counterpart department that the collaboration model would likely result in a 'very close' relationship."

 

Ultimately, the dust settled—on December 26, 2023, Gracell and AstraZeneca formally announced a definitive acquisition agreement. The acquisition was completed on February 22, 2024, with a total transaction value of US$1.2 billion. This acquisition was a landmark event, making Gracell the first Chinese biopharmaceutical company to be fully acquired by a multinational pharmaceutical company.

 

Cao believes that M&A is the ultimate path in BD. Compared to partnership models, M&A provides a one-time significant monetization, delivering returns to early investors and the founding team, and also represents the external market's high recognition of the company's comprehensive value.

 

More importantly, after being integrated into an MNC system, the company's products can gain global promotion, commercial rollout, and international market reimbursement support. For technology platform companies, acquisition may offer a larger stage, not an ending—it is the beginning of a new journey.

 

However, when the acquisition news broke, employees panicked: "The company has been sold—will we lose our jobs?" Cao reassured them: "AstraZeneca didn't just buy a product; they bought a team that can execute. Otherwise, why buy the company?"

 

In the end, almost all Gracell employees in China were retained—except for U.S. employees whose roles were tied to public company functions—and their work locations did not change. For the R&D-focused Gracell team, research funding was secured, and they gained access to global clinical, regulatory, BD, and market resources.

 

In March 2026, AstraZeneca announced it would construct a dedicated cell therapy commercial manufacturing and supply center in Shanghai Lingang to commercialize and supply autologous CAR-T therapies for China and other Asian markets, including AZD0120 (GC012F). Additionally, an AstraZeneca Gracell Cell Therapy Innovation Center will be established in Zhangjiang, covering early research, viral vector and plasmid development, analytical testing, clinical production, and regulatory support.

 

Leveraging the resources and system from the Gracell acquisition, with this new round of investment, AstraZeneca will become the first MNC in China with end-to-end cell therapy capabilities, constructing a complete cell therapy system from source innovation to global translation.

 

TONACEA 05: Epilogue – The Lonely Essence of Entrepreneurship

 

When his new book was published, Cao designed the cover himself: a solitary figure, carrying a heavy load, climbing upward. He didn't choose a DNA double helix, nor laboratory glassware. He chose that lonely silhouette because, he said, that is the entrepreneur. "A founder CEO is very lonely."

 

There is a small story: after reading the book, a former CBMG employee said to him, "Back then, when you stopped paying yourselves, we had no idea."

 

This probably captures the loneliness of an entrepreneur—some mountains must be climbed alone; some hardships must be swallowed alone. Employees don't know, family may not understand, and even investors and boards may have moments of doubt. But that solitary brave soul must continue climbing upward.

 

Albert Camus wrote in The Myth of Sisyphus: "The struggle itself toward the heights is enough to fill a man's heart. One must imagine Sisyphus happy." The boulder rolls down again and again, yet is pushed back up the peak again and again. No audience, no applause, not even an endpoint. But Sisyphus knows that his meaning lies not at the summit, but in the act of climbing itself.

Is the path Wei Cao has walked any different?

 

From CBMG to Gracell, he faced countless choices and temptations, endured countless sleepless nights, and ultimately distilled all of this into calm, composed words on the page. He said, "To pursue what you believe in to the utmost of your ability—that is success."