Cetagliptin: A Best-in-Class DPP-4 Inhibitor for Type 2 Diabetes Nears Commercialization as SinoTec Biopharma Files IPO

Last month, Shengshi Taike Biopharmaceutical Technology (Suzhou) Co., Ltd. stated in its announcement of the completion of its Pre-A financing round that its flagship product, Shenggelietin, is expected to become a best-in-class product.

Shenglietin is a novel glucose-lowering agent belonging to the incretin-based dipeptidyl peptidase-4 (DPP-4) inhibitor class. Since Merck & Co. launched sitagliptin, the world’s first DPP-4 inhibitor, in the U.S. market in 2006, DPP-4 has become one of the most prominent targets in the development of new antidiabetic drugs. Within just a few years, several top-10 pharmaceutical companies have developed multiple “gliptin” agents that represent iterative upgrades over sitagliptin in terms of efficacy, formulation, and side-effect profile.

In China, although five imported gliptin drugs have been launched and included in the national medical insurance coverage, DPP-4 remains the most fiercely contested battlefield among the country’s most R&D-intensive pharmaceutical companies. According to incomplete statistics from VCBeat, more than 10 pharmaceutical companies, including Hengrui Medicine, Salubris, CGeneTech, and Haisco Pharmaceutical, have advanced 12 domestically developed gliptin new drugs into clinical trials, making the competitive landscape exceptionally intense.

However, Dr. Yu Qiang, founder of CGeneTech, emphasized that the phrase “promising to become Best in Class” was carefully considered before being included in the press release. Recently, VCBeat conducted an exclusive interview with Dr. Yu, in which he shared his entrepreneurial journey and the basis for his confidence in Shenglietin.

Like most entrepreneurs currently active in the new drug sector, Dr. Yu Qiang bears the hallmarks of an overseas returnee with advanced degrees and extensive practical experience. What sets him apart is that his first action upon returning to China was not to seek a startup direction or angel investment, but to file for an invention patent for the precursor molecule of Shenggelietin, the drug he brought back.

In 2009, Yu Qiang returned to China with funding and his team. In 2010, he established his new company, CGeneTech, at the Suzhou Industrial Park BioBAY (BioNano Park). At that time, the young BioBAY was just getting started. The professionalism and enthusiasm of its team impressed Yu Qiang, who described his initial impression of settling in BioBAY as a sense of security. “We visited many industrial parks across China, and felt that BioBAY was a place where we could realize our vision.”

During his nine years at BioBAY, Dr. Yu experienced the darkest moments when funding for new drug development was scarce, as well as the joy of advancing Shenggelieptin from a drug precursor molecule with a molecular weight of less than 400 to a novel hypoglycemic agent that successfully completed a Phase I clinical trial with an exceptionally large sample size of 194 subjects. Today, CGeneTech has become a renowned small-molecule drug developer in China, establishing a development pipeline that spans Class 1 innovative drugs, a Class 2 flash-release formulation platform, and Class 3 first-to-market generic drugs, encompassing a product portfolio targeting various indications including cancer, diabetes, psychiatric disorders, and rare diseases.

Yu Qiang earned his bachelor’s degree in Chemistry from Peking University and holds a Ph.D. in Chemistry from the University of Kansas. He completed his postdoctoral research at the University of Kansas under the supervision of Professor Ronald Borchardt, former President of the American Association of Pharmaceutical Scientists (AAPS), developing unique insights into the evaluation of drug bioavailability.

Before returning to China, Dr. Yu founded a new drug fragment molecule company in the United States, providing early-stage research and development services for drug molecules to large pharmaceutical and biotechnology companies in the U.S.

In late 2006, sitagliptin (generic name: Januvia) received approval from the U.S. Food and Drug Administration (FDA) for market launch. For type 2 diabetes, which still lacks a mature curative treatment, the introduction of the targeted therapy sitagliptin was undoubtedly a landmark event. Sitagliptin became one of the fastest-growing new drugs in terms of post-launch sales and the fastest new drug in history to achieve annual sales exceeding $1 billion, capturing over 15% of the diabetes medication market in the United States. Subsequently, pharmaceutical companies such as Novartis, Bristol-Myers Squibb, Eli Lilly, and Takeda Pharmaceutical launched their own DPP-4 inhibitors with the same mechanism of action, including vildagliptin, saxagliptin, alogliptin, and linagliptin.

At that time, Yu Qiang, who was engaged in the research and development of drug precursors, also began to focus on DPP-4 (dipeptidyl peptidase-4) inhibitors. After a meal, the small intestine secretes incretins such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which promote insulin secretion by β-cells, thereby lowering blood glucose levels. However, DPP-4 present in the bloodstream degrades GLP-1 and GIP, rendering these incretins ineffective—a condition commonly observed in patients with type 2 diabetes. DPP-4 inhibitors can block the activity of DPP-4, sustain the effects of incretins, and prevent postprandial hyperglycemia in patients with type 2 diabetes.

After conducting his research, Yu Qiang discovered that modifying the right-hand moiety within the two-part molecular structure of sitagliptin significantly enhanced its DPP-4 inhibitory activity. Leveraging his company’s platform, he subsequently designed more than 20 adjusted precursor compounds of DPP-4 inhibitors and marketed them externally. These precursor compounds, which served as crucial “ammunition” for U.S. frontline researchers in the development of DPP-4 inhibitors, became bestsellers upon launch, generating substantial income for Yu Qiang.

However, making money was not his purpose in selling these precursor compounds. Yu Qiang hoped to determine the most promising DPP-4 inhibitor precursor compound structure through feedback from the professional market. Two months later, he identified the structurally optimal DPP-4 inhibitor precursor compound under the then-existing conditions, which was the predecessor of Shenggridiptin.

It is often said that a pharmacologist resides within every chemist’s heart. Yu Qiang swiftly concluded his career in the United States to devote his full energy to studying the druggability of this precursor compound. However, the journey from a precursor compound to a lead candidate, and further through preclinical and clinical studies, demands extensive drug development efforts. To this end, Yu Qiang partnered with Mr. Ding Juping, who had independently completed the R&D and regulatory submission for dozens of national-level new drugs, to co-found the venture. Mr. Ding, who holds a Bachelor’s degree in Chemistry from Peking University and a Master’s degree in Medicinal Chemistry from Peking Union Medical College, accelerated the preclinical research of Shenggliptin with his expertise.

“It’s very easy to be different, but very difficult to be better.” Achieving “Best in Class” status has been Dr. Yu Qiang’s overarching requirement for Shengglitiptin from the outset.

In 2016, CGeneTech completed preclinical head-to-head comparative studies of Shenggliptin and Sitagliptin, evaluating efficacy, safety, half-life, toxicology, and pathology. The results demonstrated significantly superior performance compared to Sitagliptin, leading to the initiation of Phase I clinical trials in early 2018.

In July 2019, the Phase I clinical trial featuring a head-to-head comparison between Shenglietin and Sitagliptin was completed. Dr. Yu Qiang told VCBeat that opting for a head-to-head comparative study against a star DPP-4 inhibitor like Sitagliptin during Phase I clinical trials was indeed a highly risky approach. Failure to obtain trial data demonstrating superior glycemic efficacy and safety compared to Sitagliptin would effectively spell the end of Shenglietin’s new drug development journey.

However, Dr. Yu had sufficient confidence in Shenglietin: “Our goal is to develop a best-in-class drug, which means we must outperform the leading competitor.” In 2016, sitagliptin accounted for half of the DPP-4 inhibitor sales in key hospitals across China. Head-to-head comparative data against sitagliptin would therefore carry significant market persuasiveness. At his insistence, the Phase I clinical trial of Shenglietin enrolled 194 subjects and completed comparative studies on safety, efficacy, and drug-related parameters.

Phase I clinical trial data indicate that a 50 mg dose of Shenggliptin achieves DPP-4 inhibitory activity equivalent to that of a 100 mg dose of sitagliptin. Administered once daily, Shenggliptin reaches peak plasma concentration within 1–2 hours post-dose and exhibits a longer half-life than sitagliptin, thereby sustaining stable glycemic control over a prolonged period.

In safety studies, data indicated that the adverse effects of Shenggliptin on patients’ bodies were virtually undetectable, with an incidence lower than that observed in both the placebo group and the sitagliptin group. As diabetes requires long-term pharmacotherapy, safety is the primary consideration for physicians when selecting medications for prescription. Furthermore, although Shenggliptin has a long half-life, no accumulation of residual drug in the body was observed in Phase I clinical trials.

In the verification of drug interactions between Shengliptin and metformin, the most widely used non-insulin antidiabetic drug in China, no drug interaction was observed between Shengliptin and the latter.

Dr. Yu Qiang pointed out that although domestic pharmaceutical companies have been conducting research on new domestically produced DPP-4 inhibitors for a considerable period, there have been few breakthroughs, with drug safety control becoming the biggest bottleneck in advancing clinical studies. “Among these, rash is a side effect widely observed with domestically produced DPP-4 inhibitors and has remained unresolved.” However, among nearly 200 patients who completed Phase I clinical trials of Shenggelietin, none developed a rash. It was this impressive Phase I clinical trial data that enabled CGeneTech to initiate late-stage clinical trials of Shenggelietin. CGeneTech is set to become the fastest-moving developer of new DPP-4 inhibitor drugs in terms of clinical progress among its domestic peers.

Diabetes is one of the most prevalent epidemic diseases globally, with China having the largest number of diabetic patients worldwide. Statistics show that by 2017, the number of diabetic patients in China had reached 114 million. As the prevalence rate transitioned from an outbreak phase to a stable phase, a substantial backlog of existing patients accumulated. However, the domestic diabetes drug market exhibits unique characteristics: fewer than one-quarter of diagnosed patients adhere to medication regimens, while drugs with significant side effects, such as insulin and biguanides, remain mainstream in the market. Data indicates that in prescription practices for diabetes treatment at key public hospitals in China, the utilization rate of novel hypoglycemic agents—including DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors—is below 10%.

As novel agents such as DPP-4 inhibitors continue to be included in the National Essential Medicine List and various treatment guidelines, their market demand will gradually be unleashed.

Unlike new drug companies founded by biologists and pharmacologists that focus on vertical research in specific therapeutic areas, Dr. Qiang Yu’s CGeneTech boasts a more diverse drug development pipeline.

“Survival is the most critical issue for innovative drug companies.” New drug development requires massive capital investment and spans a long duration. Relying solely on external financing can easily lead to the stagnation of drug development under immense cash flow pressure. In Dr. Yu’s view, abandoning pipelines under development not only deals a fatal blow to the company itself but also constitutes irresponsibility toward investors.

Looking back years later, the decision to focus on the R&D and sales of generic drugs with high technical barriers not only generated cash flow for the company, helping it survive the challenging period from 2014 to 2016 when R&D investment was at its peak, but also enhanced the team’s R&D capabilities. After honing their skills through generic drug development, CGeneTech’s technical staff acquired substantial foundational capabilities in drug R&D. “Rather than training the team using the most cutting-edge technologies, it is more effective to leverage relatively mature drugs and technologies.” Currently, several of CGeneTech’s first-to-market generic drugs for rare diseases have been licensed out or entered clinical trials.

Dr. Yu Qiang pointed out that, subsequently, the company will further strengthen its R&D efforts in novel anti-tumor drugs, aiming to build R&D capabilities comparable to those in its diabetes drug portfolio.