NovaBridge Biosciences Files for Hong Kong IPO, Focusing on Second-Generation Immunomodulatory Therapies for Both Cancer and Autoimmune Diseases

Nowadays, the research and development of innovative macromolecular drugs have become much more mature, making it one of the most active and highly competitive sectors in the pharmaceutical industry. Its applications continue to expand, yet it still faces numerous bottlenecks.

For instance, in the field of novel oncology drugs, monoclonal antibody therapies represented by PD-1 inhibitors still fail to effectively address tumor drug resistance. In terms of drug development, large-molecule drugs are characterized by complex structures and high molecular weights, imposing more stringent requirements on expression systems and purification processes. Furthermore, overcoming challenges related to formulation stability and injectability remains a significant hurdle.

To overcome these bottlenecks, numerous innovative pharmaceutical companies are adopting diverse strategies to research and develop next-generation large-molecule drugs. A wider array of novel therapeutic modalities, such as bispecific antibodies and antibody-drug conjugates (ADCs), is emerging, with the aim of further enriching treatment options and providing new therapies for patients. Shenzhen Kangqiao Biopharmaceutical Co., Ltd. is one of the companies striving to identify new breakthroughs in disease treatment amid this trend.

Shenzhen Kangqiao Biopharmaceutical Co., Ltd. was established in 2021 and is dedicated to the development of novel macromolecular drugs targeting macrophages, particularly tumor-associated macrophages (TAMs); innovative anti-tumor therapeutics that activate T lymphocytes; and first-in-class new drugs specifically targeting regulatory T cells (Tregs) and natural killer (NK) cells. Driven by continuous innovation, Kangqiao Biopharma aims to translate cutting-edge science into clinical practice by developing First-in-Class and Best-in-Class novel therapies for a range of refractory conditions, including advanced metastatic malignancies that are inoperable and resistant to radiotherapy/chemotherapy, as well as autoimmune diseases.

In 2021, Dr. Feisha Zhao returned to China from the United States and founded Shenzhen Kangqiao Biopharmaceutical Co., Ltd. in Shenzhen, a company dedicated to the research and development of innovative macromolecular drugs, serving as its Chairman and CEO.

Prior to returning to China, Dr. Zhao conducted postdoctoral research at Yale University in the United States, focusing on immunology, immune network theory, and the application of novel antiviral drugs. He subsequently held positions at major U.S. pharmaceutical companies, including Eli Lilly and Merck & Co., where he participated in and led pipeline development targeting new drug targets. Dr. Zhao conducted in-depth research and exploration of the novel immune checkpoint LIGHT, and later initiated new drug development programs targeting LIGHT, GITR, and other related targets. Currently, his pipeline has entered the clinical development stage in the United States.

During Dr. Zhao’s tenure at Merck & Co., no PD-1 inhibitors had yet been launched in China, and the domestic market for innovative large-molecule drugs was still in its nascent stage. By chance, Dr. Zhao learned that the father of her former university classmate had been diagnosed with lung cancer but lacked access to novel therapies such as PD-1 inhibitors. This experience highlighted the gaps and lag in China’s innovative drug market, planting the seed for her return to China to launch a startup aimed at developing innovative medicines to provide new treatment options for Chinese patients. Guided by this original aspiration and leveraging the extensive practical experience in new drug development and management capabilities she had accumulated in the United States, Dr. Zhao returned to China and established Kangqiao Biopharma.

At its inception, Kangqiao Biopharmaceutical was joined by Dr. Paul Lombrosol and Dr. Wang Shaoshan as scientific advisors, thereby completing its core founding team. Dr. Paul Lombrosol earned his medical degree from Harvard Medical School, conducted postdoctoral research in the laboratory of Nobel Laureate Dr. Greengard, and currently serves as the Director of the Child Study Center at Yale School of Medicine. Dr. Wang Shaoshan, a postdoctoral fellow at Harvard University, formerly served as the Head of Project R&D at the U.S. pharmaceutical company Biogen. Specializing in pharmacodynamics and pharmacokinetics, he has participated in and led preclinical efficacy validation and safety toxicology evaluations for both small-molecule drugs and large-molecule biologics.

However, as a large-molecule innovative drug company founded in 2021, Kangqiao Biopharmaceutical faced fierce industry competition upon its return to China. At that time, multiple PD-1 inhibitors had already been launched in the domestic market, with numerous enterprises flooding into this sector, leading to market saturation and intense involution. R&D efforts by many companies were concentrated on a few hot targets such as TIGIT and LAG-3, resulting in low-level repetitive work in the innovative drug field. Few enterprises truly achieved international leading standards.

To build core competitiveness, Kangqiao Biopharmaceutical must identify its differentiation amidst fierce competition and develop robust innovation strategies. “Most targets such as CTLA-4 and LAG-3, which are expected to be approved as drugs in the future, function by modulating T-cell activity. Unlike previous immune checkpoints that primarily focused on T-cell regulation, these novel regulatory mechanisms may bring new breakthroughs to cancer therapy.”Kangqiao Biopharma focuses on next-generation immune checkpoint modulators, targeting novel immune checkpoints with particular emphasis on the regulatory mechanisms of tumor-associated macrophages and the modulation of targets beyond PD-1.“Dr. Zhao introduced.”

Guided by this logic, Kangqiao Biopharmaceutical aims to develop second-generation novel immunomodulatory drugs, focusing on exploring disease areas refractory to PD-1 inhibitors and identifying new pathogenic targets, thereby avoiding the intense homogeneous competition prevalent among other domestic enterprises.Dr. Zhao stated, “We recognize that different types of tumors have distinct tumor microenvironments and require targeted therapeutic approaches. Kangqiao Biopharmaceutical’s research focuses on macrophage modulation within the tumor microenvironment, which may provide new insights for treating tumors that are unresponsive to PD-1 inhibitors.”

Currently, Kangqiao Biopharma has ten drug candidates in its pipeline, nine of which target malignant tumors and one targets autoimmune diseases.

In Kangqiao Biopharmaceutical’s R&D pipeline, the most advanced candidate is KQ-04, a CD47-targeted therapy for malignant tumors.

Innovative drugs targeting CD47, as a major hotspot in the field of cancer immunotherapy, have demonstrated significant potential and promising prospects for treating various malignant tumors. CD47 is an immunoglobulin-like protein widely expressed on the cell surface. By binding to signal regulatory protein alpha (SIRPα) on the surface of macrophages, it sends a “don’t eat me” signal to macrophages, helping tumor cells evade immune surveillance and clearance. Therefore, CD47-targeting agents are expected to exert antitumor effects by blocking this signal and restoring macrophage-mediated phagocytosis of tumor cells.

However, in the past two years, new CD47-targeting drugs have repeatedly failed in clinical development, facing a series of challenges. The primary concern is red blood cell (RBC) toxicity; since CD47 is also expressed on the surface of RBCs, certain antibodies may bind to them and cause hemolytic anemia. Additionally, there is the issue of T-lymphocyte toxicity, as CD47 antibodies may induce T-cell apoptosis, thereby impairing immune responses. These safety concerns have prevented new drugs in this field from ensuring patient safety or achieving an optimal balance with efficacy.

Despite these challenges, the development of CD47 antibody drugs continues to advance actively. Currently, more than 30 companies worldwide are developing CD47-targeted therapeutics, reflecting robust research activity in this field and demonstrating the industry’s optimism regarding the potential of such therapies.

In response to the drug development bottlenecks associated with CD47, Kangqiao Biopharmaceutical has adopted an innovative R&D strategy. Rather than following the trend of developing antibody-based therapeutics, the company has developed KQ-04, a receptor-ligand drug. According to Dr. Zhao,In recent animal experiments,KQ-04 precisely identifies tumor cells, thereby avoiding binding to red blood cells,nor does it cause symptoms such as anemia or thrombocytopenia,Thereby reducing side effects and improving safety. Meanwhile, KQ-04 demonstrates high efficiency in specific antigen recognition and achieves a higher response rate compared to other similar pipelines in clinical development, thereby ensuring enhanced therapeutic efficacy.

This means that KQ-04 is safer than antibody drugs and has a broader spectrum of anti-tumor effects. Kangqiao Biopharma expects to submit an IND application for KQ-04 in 2025.

In addition to KQ-04 for tumor treatment, Kangqiao Biopharmaceutical’s KQ-05 for type 1 diabetes also holds considerable promise.

Currently, the number of patients with type 1 diabetes is continuously increasing. According to a modeling study published in the international journal The Lancet, an estimated 8.4 million people worldwide had type 1 diabetes in 2021, and the number of patients with type 1 diabetes is projected to rise to between 13.5 million and 17.4 million by 2040.

However, the etiology and pathogenesis of type 1 diabetes are quite complex. It is primarily caused by autoimmune destruction of β-cells, leading to an absolute deficiency of insulin. Patients with type 1 diabetes require treatment through methods such as insulin injections or insulin pumps.

Kangqiao Biopharmaceutical’s KQ-05 originated from Dr. Zhao’s research experience on the role of regulatory T cells (Treg cells) in autoimmunity and immune tolerance during his R&D work in the United States.

In the course of his in-depth research on regulatory T cells, Dr. Zhao discovered that although these cells constitute a very low proportion of all cells (only about 0.3%), they play a crucial role in immune tolerance. “In one experiment, I isolated and cultured more than 900 regulatory T cells from 300 milliliters of blood in vitro. By day 14, these cells had proliferated unexpectedly in large numbers, which led me to reassess their potential influence in immune regulation,” said Dr. Zhao.

Impaired regulatory T cell function is implicated in the pathogenesis of various autoimmune diseases, including type 1 diabetes. In type 1 diabetes, the inability of regulatory T cells to effectively exert control leads to aberrant immune responses that attack pancreatic beta cells, resulting in reduced insulin secretion and subsequent hyperglycemia. This finding inspired Dr. Zhao to hypothesize that pharmacological activation and proliferation of regulatory T cells could yield significant therapeutic benefits for such diseases.

Guided by this concept, Kangqiao Biopharmaceutical designed and tested several drugs aimed at enhancing the function of regulatory T cells by targeting their surface receptors.KQ-05 stands out for its ability to specifically activate and proliferate regulatory T cells without affecting other types of immune cells. More encouragingly, in a mouse model of type 1 diabetes, adoptive transfer of these activated regulatory T cells resulted in significant reductions in blood glucose levels and improvement in diabetic complications, even at low doses.

KQ-05 also demonstrated excellent safety. After 21 days of observation, experimental data showed that KQ-05 induced immune homeostasis without inducing tumors or other side effects, indicating a favorable safety profile.

“In the process of developing new therapies, we recognized the potential limitations of relying solely on surgical intervention or stem cell therapy. If abnormal immune responses within the body are not effectively controlled, there remains a risk of disease recurrence. Therefore,”Our medication not only focuses on symptom relief but is also dedicated to restoring immune balance, providing patients with a more comprehensive and durable treatment regimen that achieves curative effects.“Dr. Zhao stated.”

According to reports, there are currently no comparable drugs or methods worldwide that offer a cure for type 1 diabetes, positioning Kangqiao Biopharmaceutical to take the lead. The company is planning further modification and optimization of the drug and preparing to enter the industrial production phase, with the aim of bringing this innovative therapy to more patients.

Since its establishment over two years ago, Kangqiao Biopharma has achieved significant milestones. During its early stage, the company secured support from angel investors, enabling the rapid completion of laboratory construction and the procurement of instruments and equipment. Meanwhile, it built a robust technical team and successfully established multiple technology platforms, including molecular biology, antibody generation, cell culture, efficacy screening and testing, and animal experimentation. Leveraging these platforms, Kangqiao Biopharma has completed the development of four lead drug candidates and advanced ten product pipelines, further demonstrating its R&D capabilities and diversified product strategy.

Currently, Kangqiao Biopharmaceutical has filed two patent applications, one of which has been granted while the other is under review. The company plans to file two additional patent applications in the second half of 2024. In the first half of 2024, the company’s KQ-04 and KQ-05 entered industrial-scale production. Meanwhile, screening efforts are underway for KQ-02 and KQ-03 to identify lead compounds. Furthermore, Kangqiao Biopharmaceutical has optimized the process development for KQ-04, enhancing production efficiency and stability, thereby laying the foundation for future large-scale manufacturing and cost control.

To support the company’s rapid growth and technological innovation, Kangqiao Biopharma is undertaking its next round of financing to advance its product pipeline into clinical trials and iterate its technology platform. The infusion of new capital will enable the company to further expand its R&D scope, deliver more breakthrough novel drugs, and provide patients with a broader range of therapeutic options.