Let's first look at EVO301, the drug currently attracting significant capital interest. EVO301 is a long-acting fusion protein composed of an IL-18 binding protein and an anti-serum albumin Fab-related domain.

The positive results come from a randomized, double-blind, placebo-controlled Phase IIa clinical trial. The study enrolled 70 adult patients with moderate-to-severe atopic dermatitis (AD). Patients received either 5 mg/kg of EVO301 or a placebo via intravenous injection on Day 1 and Day 28 of the study, and were followed for 12 weeks.

The study met its primary endpoint: After 12 weeks, patients in the treatment group experienced a 55% reduction in eczema severity, compared to only 22% in the placebo group. This represents a placebo-adjusted improvement rate of 33%.

Additionally, at Week 12, 23% of patients in the EVO301 treatment group achieved an vIGA-AD score of 0/1 (indicating clear or almost clear skin), compared to none in the placebo group.

BioSpace, citing comments from William Blair analysts, reported that the results for EVO301 are "very encouraging." These data position Evommune as a competitor to Regeneron and Sanofi, whose blockbuster drug Dupixent is one of the top global treatments for dermatitis.

The analysts specifically emphasized that, considering Dupixent achieved a placebo-adjusted improvement rate of 35% to 36% after 16 weeks in its Phase III trials, while EVO301 was only tested at a single dose level, "we believe that better efficacy can be achieved with a more optimized dosing regimen."

Evommune plans to test this hypothesis by advancing EVO301 into Phase IIb dose-ranging trials using a subcutaneous formulation. Concurrently, Evommune is also evaluating the candidate's potential in other indications, such as ulcerative colitis.

In the fiercely competitive red ocean of AD treatment, positive clinical news rarely creates major waves anymore. While most therapies continue to focus on established pathways like IL-4/IL-13, EVO301 has carved its own path by precisely targeting IL-18, a cytokine positioned upstream in the immune-inflammatory network.

IL-18 is a key cytokine located at the "upstream" of inflammation. It can simultaneously regulate multiple pathways, including Th1, Th2, Th17/22, and innate immunity, offering the potential for broader-spectrum immunomodulation.

This strategic choice not only makes EVO301 a highly differentiated and scarce asset within the current R&D pipeline but also opens up a deeper value proposition and imaginative space for investors.

As for Rocatinlimab, the drug abandoned by Amgen, it's quite a different story.

Rocatinlimab is an OX40-blocking antibody developed by Japan's Kyowa Kirin, featuring antibody-dependent cellular cytotoxicity (ADCC) activity. In June 2021, Amgen acquired global rights (excluding Japan) from Kyowa Kirin for a $400 million upfront payment, up to $850 million in potential milestones, and future royalties.

OX40 and its ligand OX40L are members of the TNFR and TNF superfamilies, expressed on activated T cells and antigen-presenting cells (APCs). OX40L/OX40 signaling initiated upon antigen recognition promotes T cell proliferation and survival, activating multiple T cell pathways—Tregs, Th1, Th17, Th2—through co-stimulatory signals.

In inflammatory microenvironments, OX40L expression on APCs is upregulated, further amplifying antigen-specific T cell responses and pro-inflammatory cytokine secretion. Elevated OX40L and OX40 expression is observed in various inflammatory and autoimmune diseases.

Given its upstream role in T cell activation, blocking this interaction can effectively suppress T cell-driven pathological immune responses—sparking a wave of R&D into OX40/OX40L-targeted therapies.

Rocatinlimab was one of the frontrunners in this space, with early results that were striking.

In December 2022, Amgen reported Phase II data for Rocatinlimab in atopic dermatitis: all four dose groups showed statistically significant improvements in EASI scores compared to placebo.

Buoyed by these results, Amgen aggressively advanced Phase III development. For moderate-to-severe AD alone, it launched eight Phase III trials and completed enrollment with over 3,300 patients.

In November 2025, topline data from two Phase III trials in AD (ROCKET-IGNITE and ROCKET-HORIZON) showed that both met all co-primary and key secondary endpoints.

In ROCKET-IGNITE, 42.3% of patients (300mg) achieved EASI-75 (≥75% improvement in Eczema Area and Severity Index), significantly outperforming the 13% placebo rate. 24% achieved vIGA-AD 0/1 (clear/almost clear skin), vs. 9% on placebo. Consistent efficacy was observed in ROCKET-HORIZON.

Yet despite hitting its Phase III targets, the outcome was still sobering.

As BioPharma Dive reported, Rocatinlimab didn't outperform Dupixent. Moreover, the trials showed that one in eight Rocatinlimab recipients experienced fever, and 6% reported chills—effects attributed to infusion-related reactions.

William Blair analyst Matt Phipps wrote in a report that these "relatively high rates" constitute a side effect profile that "will be a commercial challenge in chronic diseases like atopic dermatitis and may limit dosing intensity, thereby impacting efficacy."

That said, Kyowa Kirin remains committed to Rocatinlimab. The company plans to submit an NDA for AD to the FDA in the first half of 2026, followed by a submission in Japan.

In a way, the story of rocatinlimab and the OX40 target reflects the broader predicament of next-generation autoimmune therapies: unseating an established therapy is never easy.

Over the past few decades, the massive market size of the autoimmune disease field has attracted numerous pharmaceutical companies, leading to a continuous wave of new target discoveries—with the competitive landscape of the AD market serving as a prime example.

On one hand, the patient population for atopic dermatitis is enormous, providing a solid market foundation. On the other hand, the pathogenic mechanisms of the disease are not yet fully understood, and a definitive cure remains elusive, requiring patients to undergo long-term medication, which ensures sustained demand.

More critically, existing therapies generally have significant shortcomings: either considerable side effects or low patient adherence. Take Dupixent as an example—it requires administration once every two weeks. Many AD patients experience "needle fatigue," and pediatric patients, in particular, often struggle with adherence due to fear of needles.

The vast market potential, combined with unmet medical needs and Dupixent's undeniable blockbuster success, has galvanized challengers. Global pharmaceutical companies are launching offensives from multiple directions, broadly summarized as follows:

This is the most direct competition. As the world's first approved IL-4Rα monoclonal antibody, the success of durvalumab has verified the value of the IL-4R target. What the later entrants need to do is to do better: higher efficacy, lower dosing frequency, or lower cost.

Chinese pharmaceutical companies are the main force on this front. Among them, Canova's Sipulecu (CM310) was approved for the treatment of moderate to severe atopic dermatitis in adults in September 2024, making it the second IL-4Rα monoclonal antibody approved for marketing globally. Part of its development and commercialization rights have been granted to Shijiazhuang Pharmaceutical Group.

In the first half of 2025, the sales of sipuliqimab reached 169 million yuan, marking a year-on-year surge of 812%, directly driving the overall revenue of Canoy to increase to 499 million yuan. Meanwhile, the product was also included in the national medical insurance directory in December 2025, and 2026 will be its first full year of medical insurance coverage, highlighting the certainty of significant sales volume.

The NDA applications for the treatment of moderate to severe atopic dermatitis (AD) in adults have been submitted to the China Food and Drug Administration (CDE) by Canade/Simcere Pharmaceuticals for Ledibai Monoclonal Antibody (CBP-201), Zhixiang Jintai for Tailiqi Monoclonal Antibody (GR1802), and Maiji Biotechnology for Kemiqi Monoclonal Antibody (MG-K10), which are currently in the review stage.

In addition, there are still multiple competitors closely following in the domestic IL-4Rα monoclonal antibody arena: Mandociclib, developed by Kangfang Biologics, has reached the clinical endpoint; both SHR-1819 from Hengrui Pharmaceutical and SSGJ-611 from Sansun Guojian are currently in Phase III clinical trials and are expected to enter the NDA phase in the next 1-2 years.

Amidst the surging tide of new entrants, some novel targets have also demonstrated potential comparable to that of durvalumab, including JAK, OX40/OX40L, IL-13, IL-2, etc. The two aforementioned products are typical examples of this path exploration.

Regarding JAK inhibitors, two previous "head-to-head" studies between abemaciclib and upadacitinib, respectively, and durapilumab have shown that JAK inhibitors are more effective and faster in treating moderate to severe atopic dermatitis compared to IL-4R monoclonal antibody durapilumab.

However, in terms of safety, JAK inhibitors are not superior - the instructions for JAK inhibitors such as abemaciclib and upadacitinib carry black box safety warnings, indicating potential safety issues. For autoimmune patients who require long-term medication, drug safety is undoubtedly of utmost importance.

IL-13 inhibitors have also demonstrated potential. In 2023, Eli Lilly published two Phase III clinical data on the treatment of moderate to severe dermatitis with IL-13 monoclonal antibody Lebrikizumab in the New England Journal of Medicine: among patients treated for one year, the proportions of those achieving IGA0/1 were 43.1% and 33.2%, respectively, compared to only 12.7% and 10.8% in the placebo group.

On September 13, 2024, Eli Lilly announced that Lebrikizumab had received FDA approval for marketing, intended for the treatment of moderate to severe atopic dermatitis in adults and children aged 12 and above.

Nektar Therapeutics' IL-2 inhibitor, REZPEG (NKTR-358), also released Phase IIb study data on February 10th. The results indicated that REZPEG exhibits long-term durability and consistently improves AD disease symptoms during the maintenance period.

Some analysts pointed out that if these data are confirmed in further testing, REZPEG will have a significant advantage in future market competition. Compared to the twice-weekly dosing regimen of Dupixent, REZPEG, with its longer dosing frequency and durable efficacy, offers higher patient compliance.

Following the release of this research result, Nektar's stock price surged by 51.07% on the same day, with its market capitalization exceeding $1 billion. Currently, Nektar is planning to conduct a Phase III trial with a similar design. If the research results are positive, the company expects to submit an application for the marketing of REZPEG to the FDA in 2029.

Regarding the OX40/OX40L pathway, it was once regarded as a potential replacement for durvalumab, providing upstream immune regulation by regulating T cell activation. However, recent clinical data have been mixed.

However, despite Amgen's decision to abandon Rocatinlimab, a product that it had invested heavily in introducing and developing, due to "portfolio priority adjustments", this pathway still holds potential, and future optimization may focus on reducing side effects.

In addition, Sanofi's amlitelimab (an anti-OX40L antibody) also demonstrated mixed results in its Phase III clinical trials in 2025-2026. The SHORE and COAST 2 trials achieved their primary endpoints in the US analysis, but COAST 2 failed to meet some of its primary endpoints in the European analysis.

However, amlitelimab has shown skin clearance and improvement in severity, with consistent safety. Sanofi plans to submit a marketing application in 2026, emphasizing its gradual efficacy (improvement starting from week 2 and continuing until week 52). This indicates that OX40L inhibitors still have opportunities in long-term management, especially for patients resistant to Dupixent.

Beyond this, more convenient oral solutions are also sparking new imagination.

Last month, Corvus Pharmaceuticals announced that its oral ITK inhibitor, soquelitinib, demonstrated significant efficacy in Phase I clinical trials, achieving an EASI-75 response rate of up to 75%. It also showed clinical activity in treatment-resistant patients, including those who were not responsive to Dupixent and JAK inhibitors.

The data was deemed "explosive" by the market, leading to a surge of over 165% in CRVS's stock price on the same day, and a cumulative increase of more than 200% in the following month, reflecting investors' strong enthusiasm for oral AD therapy.

Despite the limited sample size (approximately 12 treated patients), this early signal has positioned soquelitinib as a potential "best-in-class" oral drug candidate, and the company plans to initiate a Phase 2 trial in the first quarter of 2026.

The annual sales of 18.8 billion US dollars are both a glory and a bull's-eye.

All challengers are eyeing this throne, and the comparison between EVO301 and Rocatinlimab reveals the harshest rule of this hunt: as a newcomer, facing the first-mover advantage of the "king of self-immunity", the only passport is "better".

This is not a romantic narrative about "subversion", but a cruel competition about "transcendence".

On the other side of the story, the protagonist on the throne is also unable to sleep peacefully.

Despite the ample width of the moat surrounding durvalumab—backed by a decade of clinical evidence, trusted by tens of millions of patients, and spanning multiple indications—every inch of it is being eroded.

Looking around, all I see are opponents - and this is the next stop for the "King of Self-Immunity": defending the throne is even harder than ascending to it.

And those surging newcomers, no matter who will ultimately make it to the table, are collectively writing a fact: after durvalumab, the treatment of atopic dermatitis will no longer have only one isolated peak.