On May 28th, Johnson&Johnson announced a final agreement with Numab Therapeutics to acquire its subsidiary Yellow Jersey Therapeutics for approximately $1.25 billion in cash, in order to acquire global rights to a first in class dual antibody, NM26, for the treatment of atopic dermatitis. The transaction is expected to be completed in the second half of 2024.
This is another dual antibody product that Johnson&Johnson has harvested within a month. Just a few days ago (May 16th), Johnson&Johnson announced an agreement with Protologix to acquire the latter for $850 million in cash. Protologix's product portfolio includes PX128, which is currently in the first phase of clinical development, and PX130, which is in the preclinical development stage. This is a bispecific antibody targeting interleukin-13 (IL-13) and TSLP for the treatment of moderate to severe atopic dermatitis (AD) and moderate to severe asthma. The transaction is expected to be completed by mid-2024.
Two acquisitions in half a month, both focused on the track of atopic dermatitis. Is this track really so charming? Regarding this, a pharmaceutical industry analyst from a securities firm told 21st Century Business Herald reporters that atopic dermatitis is one of the most common chronic inflammatory itching diseases, with a large number of patients. With the widespread demand in the atopic dermatitis market, pharmaceutical companies have become increasingly interested in research and development. With the continuous increase of clinical indications and market expansion by various pharmaceutical companies, the market size of atopic dermatitis will further expand, and the drug market for treating atopic dermatitis will become a big red ocean.
"In addition, the current market layout of companies with atopic dermatitis mainly focuses on biologically targeted therapeutic drugs and immunotherapy drugs, with fewer dual antibody drugs. However, from the perspective of the dual antibody drug track, as it is still in the early and rapid development stage, some companies with significant advantages in independent technology platforms are currently making relatively fast progress and have development potential. Johnson&Johnson's choice to enter this track also means that this track has great development prospects."
According to analysis by CICC Qixin International Consulting, the market size of atopic dermatitis drugs in China was approximately 3.77 billion yuan in 2020. Taking into account factors such as future per capita disposable income and increased per capita healthcare expenditure, this market will grow at a compound annual growth rate of 27.4% and reach approximately 12.63 billion yuan in 2025. From 2025 to 2030, the market size of Chinese atopic dermatitis drugs will grow at a compound annual growth rate of 18.4% and reach 29.43 billion yuan. According to the renowned analysis firm Global Data, the global atopic dermatitis market is expected to exceed $17 billion in 2027 with a compound annual growth rate of 11.1%. Domestic and foreign giants are laying out this track, and the $10 billion market is being leveraged.
Intense competition in the AD market
Atopic dermatitis, AD, known as the "number one" stubborn disease in dermatology, is a chronic, recurrent, and inflammatory skin disease. At different age groups, patients often have other complications such as allergic rhinitis and asthma.
Speaking of the characteristics of the disease, Professor Gu Chaoying, from the dermatology department of Huashan Hospital affiliated to Fudan University, said in an interview with the 21st Century Business Herald reporter recently that the disease has a genetic allergy quality and will come on early. The incidence rate of the disease within one year old is about 30%, the incidence rate of the disease between the ages of 1 and 7 is about 12.94%, and the incidence rate of the disease of the whole youth is about 10%. The overall incidence rate in a person's lifetime is 2%~10%; This disease is a chronic recurrent disease, which can recur repeatedly due to its stubborn eczema. Especially for patients with moderate to severe atopic dermatitis, it may recur more than nine times within a year, and nearly one-third of patients will suffer from the disease within six months; This is an inflammatory disease with abnormal immune mechanisms. The inflammatory nature of atopic dermatitis may lead to comorbidities with other allergic diseases in the body, such as rhinitis, asthma, eosinophilic esophagitis, and various other problems.
Affected by the characteristics of the disease, AD can cause severe itching on the patient's skin, which may even seriously affect their daily learning, work, and social life. Under the clinical demand, patients have increasingly high requirements for treatment goals. Correspondingly, with the continuous improvement of treatment methods, the treatment methods for AD in clinical practice are also constantly emerging.
Wanlian Securities analysis points out that currently, innovative treatment drugs for atopic dermatitis mainly include IL-4R monoclonal antibody JAK inhibitors, etc. Among them, Sanofi Dupixent is a humanized monoclonal antibody, and its sales quickly increased after FDA approval in March 2019. By 2019, Dupixent's global sales have exceeded 2 billion euros, with the US region accounting for over 80% of the market share. In June 2020, Dupixent has been approved for listing in China.
Sanofi's 2023 financial report shows that the company's annual revenue was 43.1 billion euros, a year-on-year increase of 5.3%, The IL-4R antibody has surpassed 10 billion US dollars for the first time, with sales reaching 11.556 billion US dollars. Sanofi expects Dupixent's sales to reach 13 billion euros (14 billion US dollars) in 2024.
The competition for IL-4R antibodies in China is fierce, and the products related to companies such as Kangnuoya are already in the application and listing stage. Products related to Maiji Biotechnology, Kangneide/Xiansheng Pharmaceutical have entered phase III clinical trials, while products related to companies such as Zhengda Tianqing, Hengrui Pharmaceutical, Sansheng Guojian, and Quanxin Biotechnology have entered phase II clinical trials.
In addition to IL-4R antibodies, JAK1 inhibitors are also a rising star in the field of moderate to severe atopic dermatitis. Currently, two JAK1 inhibitors worldwide have been approved for AD indications, namely Upatinib from Abervi and Abuxitinib from Pfizer. Meanwhile, a JAK inhibitor under Zejing Pharmaceuticals in China, Jackatinib, is currently in clinical stage III for moderate to severe atopic dermatitis.
"The main advantage of JAK inhibitors is that they take effect quickly, but their biggest problem is also their safety. Relatively speaking, they have a significant impact on liver and kidney function, bone marrow, blood count, etc. Once immunosuppressants are used, they need to be closely monitored for any adverse reactions." A clinical expert told 21st Century Business Herald reporters that in the drug treatment market for atopic dermatitis, immunosuppressants have significant safety hazards, which also provides opportunities for targeted biological inhibitors and even more new drugs in the future to compete.
Giant targets the dual antibody market
As Sanofi, Abbott, and Pfizer compete for the AD track, immune giant Johnson&Johnson is also unwilling to be outdone.
From the current actions, the acquisition of Numab Therapeutics experimental drug NM26 for $1.25 billion is Johnson&Johnson's second acquisition of Atopic Dermatitis in the past two weeks, highlighting the company's focus on expanding its immunological treatment.
According to public information, NM26 is about to enter Phase II research for the treatment of AD, targeting IL-4R alpha and IL-31. Compared to existing treatment methods, NM26 is a first in class dual antibody that provides unique benefits. Johnson&Johnson's acquisition of Proteology for $850 million includes a dual antibody PX128 targeting IL-13 and TSLP, which is about to enter phase I clinical development for moderate to severe AD and moderate to severe asthma.
When it comes to the market prospects of dual antibody drugs, the above analyst told 21st Century Business Herald reporters that theoretically, dual antibodies have advantages over monoclonal antibodies, such as stronger tumor killing power, better specificity, more accurate targeting of tumor cells, and reduced off target toxicity. The clinical efficacy, drug resistance, safety (using Roche Mosunetuzumab as an example with higher CRS), and even commercialization (compared to monoclonal antibodies, the price is still significantly higher, and there are certain difficulties in medical insurance) of dual antibodies still need to be observed and explored. Ultimately, the focus should still be on clinical value.
The analyst believes that for the high-quality development of the dual antibody track, in 2022, CDE has released the Clinical Research and Development Technical Guidelines for Double Specific Antibody Antitumor Drugs. For the industry, on the one hand, this has raised the entry threshold for dual antibody research and development. Under this principle, researchers are required to have sufficient research and sufficient independent innovation research and development systems, be able to optimize targets and structural design during the project initiation stage, and grasp key issues such as risk control/drug delivery strategies during the clinical research stage. This has also to some extent raised competitive barriers for leading enterprises that are making rapid progress; On the other hand, product development needs to combine clinical needs to find ideas to "solve treatment problems that cannot be solved by monoclonal antibodies, and bring clinical benefits that monoclonal antibody treatment does not have", such as the problem of monoclonal antibody drug resistance, segmented indication scenarios that have not yet been covered, and challenges to existing SOC.
"However, dual antibodies also face many challenges from research and development, production to commercialization. From a production technology perspective, it is mainly necessary to break through the technical barriers of poor drug performance and low industrial efficiency of dual antibody molecules. In addition, overall, the biggest challenge in the research and commercialization of dual antibodies is how to comprehensively judge the market prospects of drugs from multiple factors such as product efficacy, indications, competitive landscape, and drug prices." said the aforementioned analyst.
However, based on market performance, 2023 is the year of the outbreak of dual antibodies, with Roche, Abbott, Johnson&Johnson, and Pfizer all having their dual antibody products approved for market launch. Domestic dual antibodies have not stopped catching up, and pharmaceutical companies such as Corning Jerry Pharmaceutical, Zejing Pharmaceutical, Rongchang Biotechnology, China Biopharmaceutical, Hengrui Pharmaceutical, and Shiyao Group are all accelerating their layout. Industry insiders have stated that the market is expected to enter a concentrated harvest period in 3-5 years. The dual antibody track has entered a period of tremendous changes, and more pharmaceutical companies will take the train of this era in the future. As for whether dual antibody drugs can achieve good performance in the market and whether Johnson&Johnson can achieve good performance in the AD track with dual antibody products in the future, market validation is still needed.