Shou Jianyong, Founder and CSO of Ennovabio: A Disease-Mechanism-Based Strategy for Developing Therapeutics Targeting Diabetic Complications
Currently, there are numerous diabetes medications available on the market; however, the low rate of achieving treatment targets remains a significant challenge. There is still a considerable distance to go before diabetes can be cured, and the development of new antidiabetic drugs continues to face substantial obstacles.
On October 17, at the 2019 Yangtze River Delta Innovative Pharmaceutical Science Forum, Dr. Shou Jianyong delivered a speech titled “Drug Development Strategies for Diabetic Complications Based on Disease Commonalities.” VCBeat has compiled and edited the highlights of his presentation.
Dr. Shou Jianyong is the Founder and Chief Scientific Officer (CSO) of Yinuo Pharmaceuticals. He previously established and led Novartis China’s Regenerative Medicine Division, served as Head and Director of Neuroimmunology Biology at GSK, and held the positions of Head of Biology and Senior Director at Eli Lilly’s China R&D Center. He has achieved multiple world-class original accomplishments across various therapeutic areas, including oncology, stem cells, regenerative medicine, metabolism, and neurology. Dr. Shou has led or participated in more than 10 Class 1.1 novel drug projects, several of which have entered clinical trials, including the world’s first TGF-βR1 inhibitor and the first gene therapy for hearing loss.
Dr. Shou Jianyong, Founder and CSO of Yinuo Pharmaceuticals
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia and is primarily classified into three types. The first is type 1 diabetes, which results from the body's inability to secrete insulin properly. The second is type 2 diabetes, in which patients fail to respond effectively to insulin; this is the most common form of diabetes. The third is gestational diabetes, caused by decreased insulin sensitivity during pregnancy, and it has a higher incidence rate among Asian populations.
In addition, a significant proportion of the population falls into the prediabetes category. Their blood glucose levels are higher than normal, yet they do not exhibit symptoms of diabetes nor meet the diagnostic criteria for the disease; however, they face a substantially elevated risk of progressing to diabetes.
Epidemiological statistics show that in 2015, there were 415 million people with diabetes worldwide, including over 100 million patients in China. In recent years, the incidence of diabetes in China has risen rapidly; in the 1980s, the prevalence was less than 1%, but it has now climbed to 11%.
Low Treatment Target Attainment Rates Remain a Major Challenge in Diabetes Management
Compared with developed countries, China has relatively low rates of diabetes awareness, treatment, and glycemic control. Diabetes is a highly complex disease; patients typically present with one to two complications, and the incidence of various diabetic complications rises progressively with disease duration, posing a serious threat to public health.
Comprehensive management is required after a diagnosis of diabetes. Diabetes management should adhere to five key principles: diet, exercise, education, blood glucose monitoring, and medication.
When it comes to diabetes medications, there are several points worth noting.
First, there is a wide variety of diabetes medications currently available on the market. Although their mechanisms of action differ, they all demonstrate significant efficacy in blood glucose control.
Second, personalized treatment is crucial because each patient’s disease progression, blood glucose levels, and complications vary.
Third, diabetes is a slowly progressing condition; as the disease advances, timely medication adjustments or combination therapy are required to effectively control its progression.
With so many diabetes medications available on the market, does this mean there is no need to develop new drugs? The answer is no. This is because the low rate of achieving treatment targets remains a major challenge in current diabetes care, and sustaining the long-term efficacy of medications poses another significant hurdle.
Currently, diabetes remains incurable, and available medications on the market are unable to control the fundamental pathogenesis of the disease. Consequently, patients’ conditions gradually deteriorate, leading to numerous complications.
However, given the abundance of diabetes medications already on the market, the threshold for developing new antidiabetic drugs has become increasingly high.
In the past two years, most new drugs approved by the FDA have been oncology-related, with very few approvals for diabetes or metabolic disorders. This is not due to a lack of R&D efforts by pharmaceutical companies; in fact, this remains a significant area of research. Rather, the development of diabetes medications is exceptionally challenging. While this represents a pain point for the industry, it also presents an opportunity for us.
Yinuo Pharmaceuticals is focusing on innovative drugs for the treatment of diabetic complications. Patients with diabetes have a very high risk of developing complications; in some cases, death is not caused by hyperglycemia itself, but by various complications. Elevated blood glucose levels lead to metabolic disorders and excessive oxidative stress, resulting in inflammation and cellular damage. Cellular damage in different tissues gives rise to distinct complications, such as diabetic foot and cardiovascular and cerebrovascular diseases.
Taking diabetic nephropathy as an example, the incidence of this complication exceeds 20%, and the number of patients with diabetes complicated by chronic kidney disease in China is approximately 25.3 million. However, there are currently no effective pharmacological treatments available. Therefore, we believe that the market for diabetic complications holds significant promise.
Drug Development Targeting Common Mechanisms of Complex Diseases
Developing drugs for diabetic complications is not easy.
Diabetic complications are diverse, and the disease mechanisms are highly complex. The lack of biomarkers for some complications and the absence of biological models for others pose enormous challenges to drug development.
In addressing complex diseases, Enno Biopharma’s strategy is to identify commonalities within their individual characteristics. Accordingly, we have formulated a drug development strategy based on the shared pathogenic mechanisms of these diseases, aiming to achieve comprehensive control over complex disease symptoms and deliver substantial clinical benefits. Furthermore, by leveraging these common pathogenic mechanisms, we can identify key regulatory mechanisms of signaling pathways, thereby uncovering new therapeutic indications for our drugs and mitigating R&D risks.
In new drug development, target selection is of paramount importance. The relationship between diseases and targets is not a simple linear one; Anno Pharma has established various models and computational methods to assist researchers in identifying suitable targets within complex disease mechanisms.
Innovent Biologics has constructed a regulatory network of disease mechanisms through genomics. This approach allows us to assess whether our understanding of diseases is accurate and whether our methodologies are feasible. Currently, we have conducted extensive analyses on conditions such as non-alcoholic steatohepatitis (NASH), diabetic kidney disease (DKD), and diabetic eye disease. By identifying commonalities across these analyses and uncovering similarities among different diseases, and combining these insights with further target evaluation, we have initiated drug development programs.
For example, Yinnuo Pharmaceutical is currently conducting a project related to diabetic eye disease. Diabetic eye disease has become a leading cause of blindness, with highly complex pathogenic mechanisms and no effective treatments currently available, representing a significant unmet clinical need in China.
InnoBio Pharmaceuticals is developing a novel drug targeting a specific amine oxidase for the treatment of diabetic eye disease and other diabetic complications. This target aligns closely with the complex pathogenesis of diabetic eye disease and holds potential for drug development across multiple indications, including pulmonary fibrosis and fatty liver disease. Currently, no drugs targeting this mechanism have been approved globally. Our project has made substantial progress, and we plan to file for clinical trial approvals in both China and the United States next year.
In summary, diabetes is a global health challenge, and the development of drugs specifically targeting diabetes itself is highly challenging. Targeting the common mechanistic pathways underlying complex diseases represents a novel approach to the development of therapies for diabetic complications. Ennogene Pharma aims to leverage this strategy to bring affordable innovative medicines to the vast population of patients with diabetes at an earlier date.