Translated and edited from the article originally reported by China Science Daily.
Recalling the story about her university time when she asked to skip a required English course so she could listen to a signal processing course offered by the computer science department, Bai Fang—now an associate professor at the School of Life Science and Technology and assistant director of the Shanghai Institute for Advanced Immunochemical Studies (SIAIS)—laughs a little sheepishly.
Bai (middle) and the key researchers in anti-neuroblastoma drug development: Han Qilei (left), postdoctoral researcher at SIAIS, and Cao Yu (right), doctoral student at SLST.
“I’m a professor myself now, and looking back, that was a rather unreasonable request, but that professor was very open-minded and let me take the course I was interested in. I’m very grateful,” Bai recalled, “I pursued my undergraduate degree at Dalian University of Technology for a five-year double degree in Chemical Engineering and Technology, and English. However, I soon realized I was not good at lab experiments, and found myself deeply attracted to computers. I began to study by myself, and occasionally listened to courses offered by the computer science department.”
Following her interests all the way through more than a decade of study, Bai’s focus never strayed far from “computation and medicine.” This eventually led her to specialize in drug design research using high-performance computing and AI algorithms. Recently, her team’s AI drug development platform and a type of anti-neuroblastoma candidate drug patent were exclusively licensed to a biopharmaceutical startup, Punuo Bio-Pharmaceutical. The license agreement, with milestone payments totaling 237 million yuan, has drawn wide industry attention.
Truly bringing a drug to market
Punuo has been granted exclusive commercialization rights to the ShanghaiTech’s AI drug development platform (including six sets of algorithms and software).
It is worth noting that Bai herself is a co-founder of this innovative drug startup founded in 2024. She aims to better achieve the design, development, and clinical translation of drugs targeting hard-to-drug targets.
“To me, the mission of making medicine is ingrained in my bones,” Bai said proudly, looking out through the window. Whether developing drug design methods or applying advanced algorithms in drug development, she and the team’s ultimate goal has always been to “deliver a drug to market.” The laboratory research is nothing but a beginning and the rest requires industrial support. “This is a matter of continued progress,” said Bai.
At ShanghaiTech, Bai runs two labs—one focusing on algorithms and computation, and the other on biochemical experiments related to drug development, yet the labs are still at basic research stages. “A newly designed drug in the lab typically only progresses to the lead compound optimization stage after which substantial work on druggability optimization is required,” Bai explained.
Drug design and development is a long, costly, and risky process. Even with AI’s “assistance,” new drugs must pass strict examination in the areas of safety, efficacy validations, animal testing, and clinical trials. “Especially in the later stages, development cannot continue within just a university lab,” Bai explained. “To really make a drug, industrial incubation is essential.”
Entrepreneurial science advisor
The other key figure in Punuo is its chair, Mei Jingping, a highly influential woman in China’s biopharmaceutical sector. On New Year’s Day 2024, Mei reached her retirement age—but instead of resting, she embarked on “a second entrepreneurial journey.”
Back in 2022, Mei visited Bai’s drug development platform at ShanghaiTech, saw the team’s early lead compounds, and learned of their progress on neuroblastoma inhibitors. Mei and her colleagues felt that “follow-up work was needed to move quickly” to further develop these research lines.
The two parties hit it off and decided to establish an innovative biopharmaceutical company focused on leveraging AI-driven drug design methods and chemical biology technologies to develop small-molecule drug formulations.
Bai describes Mei as possessing the calm demeanor of a seasoned leader, while she, herself tends to get anxious, being an impatient person. When problems arise, Mei always reassures her, “don’t worry, take your time,” patiently listening to the team’s technical ideas and progress, and communicating them concisely to investors. Within about a year, Punuo was ready to complete its angel round of financing.
At Punuo, Bai serves as chief scientific advisor, and is not involved in operations, so she can continue focusing on teaching and research. Beyond advancing new drug development, Bai hopes to establish sustainable platforms for drug design-related technologies.
“We combined AI algorithms to develop a series of drug design methods, but this process faces issues in further development,” Bai explained. “At the university level, all we can do is develop the methods into an online tool, free to the public, but very basic and noninteractive.” She expressed her worries, “Without further iterations in the tool, even the most advanced methods will become obsolete.” That’s why it is necessary for Bai to find a platform that can wrap these methods into software or toolkits, enabling progressive improvement, that will systematically build the drug design platform.
“Such engineering undertakings often come with repetitive tasks. Our lab aims at innovative research, so we need a company to carry these out,” said Bai.
Fearless in tackling the challenges
When it comes to the neuroblastoma inhibitor developed by Bai’s team, another important partner must be mentioned, Dr. Li Kai, director of pediatric oncology surgery at Children’s Hospital of Fudan University.
At an academic exchange between SLST and Children’s Hospital, Li showed Bai photos of children with neuroblastoma, the most lethal extracranial malignant tumor in children, with no satisfactory drugs currently available. Existing antibody drugs only partially respond, are costly, and quickly lead to drug resistance.
“Some images you never forget,” Bai recalled. As a mother herself, she told Dr. Li then and there, “We design drugs. We can do this.”
Leveraging years of drug design experience combined with cutting-edge technologies, Bai’s team quickly identified drug targets and discovered a class of small molecules that act as target protein degraders for neuroblastoma, further obtaining positive efficacy validations in multiple animal models.
“In animal models, the tumors shrank significantly and did not recur for a long time,” Bai said. They also validated the compound in animals using clinical samples from relapse patients, with equally positive results. The team is now optimizing its metabolic properties to prepare for preclinical safety evaluations.
Pediatric neuroblastoma has an incidence rate of less than one in 100,000 in China, classifying it as a rare disease. Orphan drug development often involves high costs and low expected returns, deterring many large companies. Even so, Punuo, focused on addressing unmet clinical needs, remains undeterred.