On July 22, Hong Kong-listed innovative drug company YunDingxinYao-B (01952) announced that the global phase 2b PALIZADE trial of its first-in-class drug Zetomipzomib for the treatment of active lupus nephritis (LN) has completed the first patient dosing in China.

Zetomipzomib is a novel, selective immunoproteasome inhibitor used to treat a range of autoimmune diseases including lupus nephritis, systemic lupus erythematosus (SLE) and autoimmune hepatitis. This represents not only another milestone for Zetomipzomib following clinical trial approval in China, but also means that YunDingxinYao's leading advantage in the field of kidney disease and autoimmune diseases is further strengthened.

YunDingxinYao CEO Luo Yongqing said that LN is the most common secondary immunological glomerulonephritis and can gradually lead to kidney failure, with an estimated 400,000 to 600,000 LN patients in China and a huge unmet clinical need. "We will rely on the company's strength in clinical development and registration as well as commercialization to accelerate the project and benefit Chinese patients as soon as possible."

It is noteworthy that Zetomipzomib is the third new drug for the treatment of immune kidney disease to be developed by YunDingxinYao, following Nifukang and BTK inhibitor EVER001. YunDingxinYao focuses on glomerular disease and continues to expand its product pipeline and consolidate its leadership in the field of kidney disease. China Great Wall research reports indicate that YunDingxinYao targets high-potential, low-competition tracks and builds a differentiated product line.

Lupus nephritis is a major clinical challenge, and early studies of Zetomipzomib have yielded positive results.

According to reports, SLE is a severe autoimmune disease characterized by widespread immune abnormalities and multi-organ damage, causing LN when it affects the kidneys. According to a 2020 study, Asian SLE patients have a higher burden of disease, more active disease, more renal complications, and increasing morbidity and mortality.

In the past decade or so, the choice of LN treatment plans in China has become more individualized, and the promotion and application of new immunosuppressive regimens, especially multi-target therapies, have significantly improved the LN remission rate. However, the high recurrence rate of 33%-40% has led to a large number of patients with chronic kidney damage or even end-stage renal disease, while treatment-related complications such as infection, diabetes, avascular necrosis of the femoral head and ovarian failure are important reasons for the decline in quality of life of patients, and there is an urgent need for innovative therapies.

In February 2024, the National Medical Products Administration (NMPA) drug evaluation center approved YunDingxinYao to initiate the Phase 2b PALIZADE clinical trial of Zetomipzomib for the treatment of active lupus nephritis in China. The PALIZADE clinical study is a global, placebo-controlled, Phase 2b clinical study designed to evaluate the efficacy and safety of two doses of Zetomipzomib in LN patients, with a target enrollment of 279 patients.

Different from the action of traditional direct immunosuppressants, Zetomipzomib can regulate innate and adaptive immune responses, thereby reducing inflammation-induced organ damage, which gives it the potential to treat a variety of autoimmune diseases. Data from Phase 1 and Phase 2 clinical trials have fully demonstrated the good safety and tolerance profile of Zetomipzomib in the treatment of severe, chronic autoimmune diseases.

Previous Phase 2 clinical trial data showed positive results for Zetomipzomib in the treatment of LN, with clinically meaningful overall renal response rates of 64.7% and 88.2% at Week 25 (end of treatment) and Week 37 (12 weeks after treatment discontinuation), respectively, and complete renal response rates of 35.3% and 41.2%, with average urinary protein/creatinine ratio decreasing by 57.0% and 83.0% from baseline, respectively, while estimated glomerular filtration rate remained stable during treatment.

Advantages in the field of kidney disease and autoimmune diseases are expanding, and multiple innovative drugs are in commercialization or clinical development stages.

In recent years, the field of kidney disease treatment has received industry attention. Public data shows that China has the world's largest number of chronic kidney disease (CKD) patients, with about 125 million, accounting for about 18% of the global total. The adult CKD prevalence rate in China is 10.8% and is expected to further increase.

According to the 2023 financial report, nephropathy and autoimmune diseases are the key treatment areas of Yunding Xinyao's strategic focus, and the company currently has multiple drugs in commercialization or clinical development stages. It will continue to promote the pipeline clinical development process and strengthen its leadership position in the treatment of nephropathy and autoimmune diseases. Zetozomide is Yunding Xinyao's third new drug for the treatment of immune-mediated kidney disease after Nifocus and BTK inhibitor EVER001.

"Nephropathy and autoimmune diseases are the key treatment areas of Yunding Xinyao's strategic focus. The company currently has three nephrology drugs in commercialization or clinical development stages, and we will continue to promote the pipeline clinical development process to consolidate Yunding Xinyao's leadership position in the treatment of nephropathy and autoimmune diseases," said Luo Yongqing.

Yunding Xinyao's heavyweight product, Nifocus, in the field of nephropathy is the world's first and only drug approved by the FDA for the treatment of IgA nephropathy with risk of progression. Since October 2023, the drug has been approved in Mainland China, Macau, Singapore, and Hong Kong, and the first prescription has been issued in Mainland China in May of this year, gradually benefiting five million Chinese patients. Yunding Xinyao expects Nifocus to reach its peak annual sales of 5 billion yuan in 2030.

In addition, Yunding Xinyao has also laid out EVER001 capsules - a new generation of covalent reversible BTK inhibitors, and a preclinical monoclonal antibody and other drugs. The potential therapeutic targets include 2 million membranous nephropathy patients who currently have no targeted drugs available in China, 1 million-2 million minor pathological lesions patients, as well as 0.5 million-1 million focal segmental glomerulosclerosis patients. Among them, the EVERO01 (XNWO01) clinical trial is underway and is expected to become a representative product in the field of nephropathy.

A research report by China Great Wall Securities states that currently, all globally-innovative drugs under development for the treatment of IgA nephropathy are focused on second-line treatment, and popular targets such as B-cell clearance mechanisms and complement inhibitors are fiercely competitive. Therefore, a completely new and effective drug mechanism will be the key breakthrough point for manufacturers. Currently, Yunding Xinyao's nephropathy pipeline can bring new choices to approximately 10 million glomerulonephritis patients.

In the field of autoimmune diseases, Yunding Xinyao's heavyweight product, Imiquimod, has obtained positive top-line results for its multi-center Phase III clinical trial in Asia for the treatment of moderate to severe active ulcerative colitis at both the 12-week induction period and the 40-week maintenance period. It is expected to submit a new drug application to the NMPA in the second half of this year. Imiquimod has been approved for new drug listing in the United States and Europe, becoming the first and only new generation oral drug approved for patients aged 16 and above in the European Union. It was also listed on the market in Macau in April this year. Yunding Xinyao expects Imiquimod to achieve its peak annual sales of 2 billion yuan in 2030.

"Yunding Xinyao targets high-potential, low-competition tracks and builds a differentiated product pipeline. With the gradual commercialization of major products, revenue growth is expected and the prospect of turning losses into profits is close at hand," according to the research report.