Johnson & Johnson Inks $1.25 Billion Deal for Oral STAT6 Inhibitor KP-723 in Autoimmune Diseases

On December 26, Johnson & Johnson announced that it had entered into an exclusive licensing agreement with Japanese pharmaceutical company Kaken Pharmaceutical. Under the agreement, Johnson & Johnson obtained the rights to develop, manufacture, and commercialize KP-723 globally, excluding Japan, for the treatment of autoimmune and allergic diseases. Kaken will retain commercialization rights in Japan, while Johnson & Johnson has the option to enter into a co-promotion agreement with Kaken.

Under the terms of the agreement, Johnson & Johnson will pay Kaken a $30 million upfront payment, $1.2175 billion in milestone payments, and single-digit to low double-digit percentage royalties on sales. Kaken is also eligible to receive equity investment from Johnson & Johnson Innovation.

KP-723 is a novel oral STAT6 inhibitor currently in the preclinical research stage. Kaken is expected to initiate a Phase 1 trial for atopic dermatitis (AD) next year and may also explore the drug’s application in other Th2-mediated diseases, including asthma. Subsequently, Johnson & Johnson will lead global clinical development and commercialization.

Atopic Dermatitis (AD) is a chronic, recurrent, inflammatory skin disease that commonly occurs in infants and children but can also affect adults. As patients often have comorbid allergic rhinitis, asthma, and other atopic conditions, it is considered a systemic disease. The most fundamental characteristics of AD are dry skin, chronic eczematous lesions, and intense itching, significantly impacting the patient's quality of life.

Data shows that the number of patients with atopic dermatitis worldwide reached 680 million in 2022, including 360 million children/adolescents, and is expected to reach 750 million by 2030, including 380 million children/adolescents. In 2022, the number of patients with atopic dermatitis in China reached 70.7 million, including 34.7 million children/adolescents. It is expected to reach 81.7 million by 2030, including 36.5 million children/adolescents.

The study found that the pathogenesis of atopic dermatitis is related to various cytokines, among which IL-4 and IL-13 play a central role in this process.

IL-4 and IL-13 are key cytokines in type 2 inflammatory responses and are associated with various atopic diseases, including AD, asthma, and chronic rhinosinusitis with nasal polyps (CSwNP). In AD, IL-4 and IL-13 mediate inflammatory responses by signaling through binding to the type 2 IL-4 receptor (IL-4R). They can induce immunoglobulin class switching to immunoglobulin E (IgE) in B cells and promote pruritus by stimulating afferent neurons via IL-4Rα, an important aspect of the pathophysiology of atopic dermatitis. Additionally, IL-4 and IL-13 are involved in regulating skin barrier function and suppressing the production of antimicrobial peptides, further influencing the course of AD. Therefore, IL-4 and IL-13 are not only crucial factors in the pathophysiology of AD but also important therapeutic targets for its treatment.

STAT6 is the sole specific transcription factor in the IL4/IL-13 signaling pathway and a core driver of Th2 inflammation in allergic diseases, playing a critical role in multiple physiological processes such as immune response, inflammatory reactions, and cell proliferation.

Currently, there are significant unmet medical needs in Th2-mediated diseases such as atopic dermatitis. The development of KP-723 is expected to offer new treatment options for these patients. As an oral medication, KP-723 will also provide a more convenient administration method compared to injections or topical treatments, which can improve patient compliance.

Through its collaboration with Kaken, Johnson & Johnson is able to leverage Kaken's R&D achievements in the field of STAT6 inhibitors to accelerate drug development. At the same time, Johnson & Johnson aims to further expand its focus on STAT6 to strengthen its presence in the atopic dermatitis and asthma sectors.

In recent years, autoimmune drugs have been a core business for Johnson & Johnson, with products such as Remicade (infliximab), Stelara (ustekinumab), Tremfya (guselkumab), and Simponi/Simponi Aria (golimumab) contributing significantly to its revenue.

Among them, infliximab has contributed more than $900 billion in revenue to Johnson & Johnson since its launch. Another product, ustekinumab, achieved sales of over $10 billion in 2023, also being a key pillar product for Johnson & Johnson.

However, both of these products are facing patent expiration issues. To fill the patent cliff, Johnson & Johnson is also actively seeking new breakthroughs.

In the past, Johnson & Johnson's R&D strategy in the autoimmune field mainly focused on developing oral small-molecule drugs JNJ-2113 and JNJ-1459 targeting IL-17 and IL-23, while continuously iterating therapies to optimize patient medication adherence. Now, Johnson & Johnson has begun to expand its bispecific antibody portfolio to address multiple pathogenic pathways.

Johnson & Johnson’s Two Autoimmune M&A Deals This Year Enter the Th2 Iteration Track via Bispecific Antibodies. In May this year, Johnson & Johnson completed two acquisitions. First, it acquired Proteologix for $850 million, obtaining several bispecific antibody therapies, including PX128, a bispecific antibody targeting IL-13 and TSLP, which is about to enter Phase I clinical development for moderate to severe AD and moderate to severe asthma. Additionally, Johnson & Johnson reached a definitive agreement with Numab to acquire Yellow Jersey Therapeutics, a subsidiary of Numab, for approximately $1.25 billion in cash, gaining global rights to NM26, a bispecific antibody therapy for AD.

According to incomplete statistics, Johnson & Johnson currently has about 10 drugs in development for the AD field. Based on several already marketed autoimmune products, Johnson & Johnson will continue to expand its advantages in this field, forming a group combat strategy.

In addition to Johnson & Johnson, major pharmaceutical companies such as Sanofi, AbbVie, GlaxoSmithKline, Novartis, and Vertex Pharmaceuticals are also focusing on the autoimmune field. Sanofi's IL-4R (Th2) and Johnson & Johnson's IL-12/IL-23 (Th17) have become billion-dollar products, with IL-17 and IL-23 giving rise to multiple blockbuster drugs. GlaxoSmithKline acquired Aiolos for $1.4 billion to obtain a long-acting TSLP antibody, entering the Th2 track. Sanofi has made autoimmune inflammation its absolute core, continuously engaging in multiple transactions. Lilly acquired DICE to further layout IL-17 from the perspective of small molecule alternatives, and so on.

At the same time, domestic companies are also making rapid progress. According to statistics, among nearly 80 new drug research and development enterprises listed on the A-share and H-share markets in China, 43 have entered the autoimmune track. Particularly in disease areas such as atopic dermatitis, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus, some local pharmaceutical companies have achieved initial R&D successes.

As BD deals in the global autoimmune field continue to be reached, and late-stage pipelines in China's autoimmune sector are successively approved, a new commercial era for the autoimmune field is about to begin. In the future, starting from this new market point, who can "overtake on the curve" remains to be tested by time.