World’s first anti-scar drug: Mabwell Biosciences’ IL-11 antibody targets trillion-yuan fibrosis and anti-aging markets

In the increasingly competitive field of oncology, some innovative drug companies are turning their attention to more differentiated blue ocean tracks, such as Mabwell.

Recently, Mabwell announced that the Phase II clinical trial application for its innovative IL-11 targeted monoclonal antibody drug 9MW3811, aimed at pathological scars, has been accepted by China's National Medical Products Administration (NMPA). This isThe world's first IL-11 targeted drug to enter the clinical stage in the field of pathological scar indications.

IL-11 is a key cytokine in chronic inflammation and fibrosis-related diseases. Although many pharmaceutical giants have explored this target before, Mabwell is the only one to use it for the treatment of pathological scars. Previously, Mabwell also collaborated with Calico Life Sciences on 9MW3811 to explore the application of this target in the anti-aging field.

With its globally leading layout in the IL-11 target, differentiated indication selection (pathological scarring and anti-aging), and potential FIC attributes, Mabwell is building a unique competitive advantage and commercial imagination in emerging therapeutic fields.

Blue Ocean Market, Huge Demand

As the largest organ of the human body, the skin serves as the first line of defense against external factors. Numerous destructive external stimuli, such as trauma, burns, and surgery, can lead to skin damage, with scar formation being a common result. Pathological scars are mainly categorized into hypertrophic scars, keloids, and contracture scars. Their shared histological features include abnormal proliferation of fibroblasts and excessive collagen deposition, which impair skin function. Severe scar hypertrophy and keloids not only cause significant physiological distress but also greatly affect patients' emotional well-being.

According to data from Frost & Sullivan,There are approximately 25 million patients worldwide (about 7.4 million in China) with pathological scars, and the incidence rate is continuously increasing. It is estimated that the number of patients in China will exceed 10 million by 2030. Moreover, with the improvement of residents' health awareness and the deepening of the "appearance consumption" concept, scar treatment is ushering in unprecedented development opportunities.

According to the prospectus data of Sirnaomics, the total market size for the treatment of hypertrophic scars and keloids in the United States is expected to grow rapidly in the coming years, increasing from USD 10.3 billion in 2020 to USD 12.3 billion in 2025 and further to USD 18.6 billion in 2030.

Currently, there is no standard clinical treatment for scars. Combination therapies are often used, such as surgical excision combined with radiotherapy, laser-assisted corticosteroid delivery, or the use of two or more drugs in combination. However, due to the unclear underlying mechanisms of pathological scars and the complexity and limited efficacy of existing treatments, there remains a substantial unmet clinical need.

Nevertheless, as research on the mechanisms of scar formation progresses, IL-11 has gradually demonstrated its promising therapeutic potential.

World's First: Domestic New Drug Achieves Breakthrough

In 2022, a research paper published in the authoritative international journal, Journal of Investigative Dermatology, revealed that CD39+ fibroblasts are the core effector cells in the formation of hypertrophic scars. The cytokine IL-11 secreted by these cells drives the activation of CD39- fibroblasts into myofibroblasts, characterized by increased extracellular matrix synthesis and upregulated α-smooth muscle actin expression, thereby promoting scar formation and development. Blocking the IL-11-related signaling pathway significantly reduces the number of α-smooth muscle actin-positive fibroblasts and effectively interrupts this pathological process.

This discovery provides a new technical approach for the field of scar treatment.

Currently, Mabwell's 9MW3811 is the world's first and only IL-11-targeted drug to enter the clinical stage in the field of pathological scarring.

According to publicly available information from Mabwell, 9MW3811 is a high-affinity humanized monoclonal antibody targeting human IL-11 developed by Mabwell. It effectively inhibits the abnormal activation of the IL-11/IL-11Rα signaling pathway, thereby intervening in the pathological progression of fibrosis-related diseases.

This candidate molecule exhibits higher target affinity and neutralizing activity, along with a long half-life of over one month, making it highly favorable for the treatment of chronic diseases.

Preclinical studies have shown that 9MW3811 can effectively alleviate the skin fibrosis process and reduce the volume of established scar tissue in humanized keloid animal models.

Currently, 9MW3811 has been submitted to China's NMPA for Phase II clinical trials and has been accepted. Patient recruitment is expected to begin by the end of the year. The clinical cycle for pathological scar treatment is relatively short, and the efficacy is easy to observe, allowing for rapid acquisition of human Proof of Concept (POC) data. 

IL-11, A New Target with Therapeutic Potential for Multiple Diseases

It is worth noting that the IL-11 target is not a single-function target. Its biological functions are extensive and involve multiple fields.

IL-11, a member of the IL-6 family, is a key cytokine in chronic inflammation and fibrosis-related diseases. It can reduce the transcription and synthesis of pro-inflammatory mediators such as TNF-α, IL-1β, IL-12, and IL-6 in monocytes and macrophages by inhibiting the classical NF-κB pathway. It can also induce T helper 2 (Th2) polarization, promote the secretion of IL-4, and suppress T helper 1 (Th1) polarization and the secretion of IL-12, IL-2, and interferon (IFN)-γ, thereby alleviating tissue damage. IL-11 can stimulate the secretion of chemokines with pro-inflammatory effects (CXCL1/5/6, CCL20, MCP1, IL-8) and participate in the recruitment of immune cells to the site of injury during the immune response.

In recent years, research on this target has covered fields such as fibrotic diseases, inflammatory diseases, anti-aging, pathological scars, and tumors.

Currently, there are not many IL-11 targeted drugs entering clinical trials. Among them, Boehringer Ingelheim's BI-765423 is the most advanced, having entered Phase II clinical trials for the treatment of pulmonary fibrosis in June this year.

Mabwell's 9MW3811 clinical development progress ranks first in China. Preclinical studies have shown that 9MW3811 exhibits significant efficacy in various models, including pulmonary fibrosis, and demonstrates potential application value in fibrosis-related diseases such as hypertrophic scarring and abnormal uterine bleeding.

9MW3811 has been approved globally for clinical research in advanced malignant tumors and idiopathic pulmonary fibrosis. It has completed Phase I trials in healthy subjects in Australia and China, showing good safety and a half-life of more than one month. In addition, Mabwell is also exploring the use of 9MW3811 in thyroid eye disease, skin fibrosis, renal fibrosis, liver fibrosis, cardiac fibrosis, and other multi-organ fibrotic diseases. Beyond that, MabwellMabwell has successively tapped the huge potential of its products in the two blue ocean markets of anti-aging and pathological scars, which can be described as pioneering a unique path.

In June this year, Mabwell Enters into Exclusive License Agreement with Calico Life Sciences for 9MW3811, the latter gains global rights outside Greater China, and Mabwell obtains $25 million upfront payment, with milestone payments up to $571 million, as well as tiered royalties based on the net sales of licensed products.

Calico was founded by Page, Google's co-founder, in 2013. He appointed former Genentech CEO Arthur Levinson as its CEO. Calico has long focused on innovative anti-aging therapies and has a strong research foundation in anti-aging studies. This collaboration signifies international giants' recognition of 9MW3811's potential in anti-aging.

Innovation does not always mean that one should be the first to discover a target. Rather, it is about whether one can be the first to discover a new connection between the target and a disease, and successfully translate it into a treatment. Mabwell's ability to keenly capture the therapeutic potential of IL-11 targeted drugs in blue ocean areas such as pathological scarring and anti-aging reflects its outstanding scientific insight and strong R&D translation capabilities.

The Phase II clinical trial of 9MW3811 is planned to initiate patient enrollment by the end of 2025. With the advantage of a shorter clinical cycle, this drug is expected to rapidly obtain human POC (Proof of Concept) data. Once successful, it will become the world's first IL-11 targeted therapeutic drug for pathological scars, filling a market gap while opening up broader market opportunities for Mabwell in areas such as multi-organ fibrosis and anti-aging. With such groundbreaking progress, China's innovative drugs are increasingly demonstrating significant influence on the global pharmaceutical stage.

Source: Qiu Shi Pharmacy