At the annual premier event of the immunology community – the American Association of Immunologists (AAI) Annual Meeting – the spotlight has long been dominated by global biopharmaceutical giants and large-molecule innovative drug companies. However, at the 2026 Boston meeting, the cross-industry appearance of tech giant ByteDance drew widespread attention. At this traditional stronghold of immunology, ByteDance publicly disclosed a preclinical-stage IL-17 small molecule inhibitor. Notably, this is not a conventional Fast-Follow pipeline, but the world's first "pan-spectrum" IL-17 small molecule inhibitor. The project demonstrates, using its in-house AI technology, the first achievement of comprehensive blockade of the IL-17 family (AA/AF/FF) at the small molecule level. The disclosure of this core pipeline not only signifies a rare breakthrough in target mechanism but also provides a highly compelling substantive endorsement of the industry trend that "AI is substantially reshaping the fundamental logic of drug discovery."

It can be said that this is not merely a case of using AI to accelerate R&D efficiency, but a true example of leveraging AI to challenge "undruggable" targets and overcome industry bottlenecks.

TONACEA 01: Meeting Summary – The First Small Molecule Pan-Spectrum (AA/AF/FF) IL-17 Inhibitor

This was an oral presentation delivered at AAI 2026. According to details disclosed at the conference, Anew Therapeutics, ByteDance's AI-pharma subsidiary, has successfully developed the world's first oral small molecule pan-spectrum inhibitor of IL-17A and IL-17F.

• Pan-Spectrum Coverage: It breaks through the limitation of previous small molecules, which could only target IL-17AA and AF, achieving comprehensive inhibition of IL-17AA, IL-17AF, and the previously undruggable IL-17FF dimer.

• High Potency: Cellular functional inhibition (Ki) reaches picomolar (IL-17AA) to low nanomolar (IL-17AF/FF) levels. The lead molecule mentioned, AN-5162, has a Ki of 6.2 nM for IL-17FF and <0.1 nM for IL-17AA, demonstrating over 10-fold higher potency compared to other small molecule inhibitors. In vivo efficacy is equivalent to the benchmark dual-targeting antibody Bimekizumab.

• Drug-like Properties: Exhibits favorable oral exposure profiles across multiple species, providing a solid foundation for advancement into clinical stages.

TONACEA 02: Clinical Potential Analysis – Breaking Mechanistic Limitations, from "Partial Substitution" to "Mechanistic Replacement"

The IL-17 pathway holds a central position in the treatment landscape of autoimmune diseases such as psoriasis and ankylosing spondylitis. For a long time, while small molecule drugs offer advantages in oral convenience and patient compliance, they have been constrained by incomplete mechanistic coverage. This newly disclosed pan-spectrum small molecule progress offers a novel technological possibility to address the mechanistic shortcomings of small molecules.

01、The Interplay Between Mechanistic Advantages and Druggability Challenges

In clinical practice, the trend that "dual blockade of IL-17A and IL-17F leads to superior efficacy" has become widely recognized. Multiple head-to-head clinical trials, notably with the benchmark dual-targeting antibody Bimekizumab, repeatedly demonstrate that comprehensive neutralization of all three forms (IL-17AA, AF, and FF) achieves faster and deeper skin clearance (e.g., higher PASI 100 response rates) and inflammation relief than blocking IL-17A alone. The underlying biological rationale is that IL-17FF often has higher expression abundance in lesional tissue and plays a more sustained role in maintaining inflammation.

Given the vast market potential of oral drugs, small molecule IL-17 inhibitors have been a hot area in autoimmune R&D, with intensive efforts from leading MNCs such as Eli Lilly, Sanofi, Novartis, and AbbVie. However, limited by the constraints of traditional structure-based design, previous small molecule candidates (e.g., DC-853) typically could only target IL-17A (acting on IL-17AA or partially on IL-17AF). In particular, the IL-17FF homodimer, due to its unique protein sequence and lack of a canonical binding pocket, has long been an insurmountable development barrier for small molecule drugs.

Consequently, before the disclosure of this achievement, no small molecule had been reported that could efficiently inhibit IL-17AA, AF, and FF simultaneously.

02、Evolution of Treatments and Realistic Assessment

The emergence of this pan-spectrum small molecule pipeline offers a new approach to breaking the long-standing R&D deadlock. If such molecules advance successfully through clinical development and demonstrate safety, they could potentially combine the mechanistic advantages of dual-targeting approaches with the high patient compliance associated with oral administration.

Compared to previous single-target small molecules that offered only "partial substitution" or a "follow-on" approach to the large molecule market, the "mechanistic replacement" enabled by this pan-spectrum blockade suggests a more profound potential for industry impact. If successfully developed into a drug, it could substantially reshape the current therapeutic hierarchy for autoimmune diseases, providing a more powerful tool for improving long-term patient medication habits.

In the treatment landscape for autoimmune diseases (such as psoriasis and ankylosing spondylitis), the IL-17 pathway is absolutely central. For a long time, while small molecule drugs offered oral convenience, they were often limited in mechanistic coverage. This breakthrough truly fills the last remaining mechanistic gap for small molecules in this area.

TONACEA 03: Analysis and Reflections – Tech Giants' "Disruption and Restructuring" of the Pharmaceutical Industry

Based on the disclosed pipeline progress, from an industry observer's perspective, several key signals are emerging that presage a shift in the fundamental logic of drug discovery and development:

01、Breaking Traditional R&D Bottlenecks: Generational Advantage of Foundational R&D Paradigms

The development history of the IL-17 target epitomizes the scenario where large molecules advanced triumphantly while small molecules struggled. The clinical value of "pan-spectrum (AA/AF/FF) inhibition of IL-17" was recognized early by both academia and industry. However, traditional pharmaceutical giants, constrained by their screening tools and empirical science, were unable to achieve substantial breakthroughs against the difficult PPI (protein-protein interaction) target.

The fact that this rare pan-spectrum inhibitor did not emerge from an established MNC, but was instead first cracked by a technology company with expertise in algorithms, essentially reflects the generational advantage of a newer R&D paradigm. This suggests that for exploring extremely challenging chemical space, the traditional pathways of high-throughput screening and empirical trial-and-error are showing signs of fatigue. Generative AI combined with advanced structural prediction models offers a more deterministic engineering solution to bridge such "undruggable" chasms.

02、"Redefine Feasibility": AI Pharma Enters the 2.0 Era

I found the homepage of the reporting unit, Anew Therapeutics. The most prominent words on the page are: "Redefine Feasibility in Medicine. Making Previously Unreachable Therapies Achievable." This is an ambitious vision: using AI to "challenge" drugs that traditional methods couldn't make.

In the past few years, the AI pharma sector has experienced a prolonged bubble period, filled with a large number of theoretical models stuck at the paper stage, as well as me-too pipelines dressed up under the guise of AI. The public disclosure of this pan-spectrum IL-17 small molecule PCC at a professional medical academic conference represents a highly substantive deliverable and proof-of-concept for the field. It demonstrates that AI can indeed play a core role in substantially expanding the boundaries of "druggability."

Objective Perspective: After Crossing the "Natural Barrier," the Clinical "Deep Water" Still Lies Ahead

As a rigorous industry observer, we must point out that preclinical molecule discovery is only the first step in the long march of new drug development. This program is still currently in preclinical stages. Whether the ultra-high in vitro activity and superior efficacy in animal models of the candidate molecules will translate into real therapeutic effects in the highly complex human body, while effectively avoiding off-target toxicity, unforeseen pharmacokinetic defects, and other safety risks, remains to be tested by stringent Phase I/II/III clinical data. For ByteDance, a cross-industry entrant, crossing the "natural barrier" of molecule discovery with AI is undeniably impressive. However, what lies ahead is the deep, unfathomable traditional long road of clinical development for new drugs.

03、Tech Giants Accelerate Penetration into the Core Arena: Reshaping the Industrial Ecosystem

Historically, the industry's perception of tech giants venturing into the pharmaceutical space has often been limited to that of "shovel sellers" – technology service providers or suppliers of auxiliary tools. However, the current global competitive landscape has profoundly changed. Tech giants, with their computational and algorithmic prowess, are reshaping the role of drug R&D in an entirely new posture.

The most representative example among these is Google's Isomorphic Labs, which not only successfully secured US$600 million in funding but also, leveraging its AI algorithms, won significant collaboration deals with established MNCs like Novartis and Eli Lilly. With ByteDance's debut of a challenging First-in-class pipeline, its strategic intention to build a world-leading AI pharmaceutical company based in China is clearly emerging. In the future industrial ecosystem, tech giants may well become a distinctive and powerful force. Relying on their computational power and algorithmic barriers, they can establish a generational advantage in areas hard to reach with traditional methods, and generate more high-value, highly promising drug pipelines. This heralds a profound redistribution of the innovation chain and decision-making power in the global pharmaceutical industry.