主要会議2日目 2026年10月21日（水） - 日本時間（GMT+09:00)

• Overcoming the "digestion barrier" through pI engineering, potency optimization, and novel delivery technologies to convert injections to tablets.
• Engineering the world’s first oral VHH-based antibody for haemophilia.
• Utilizing albumin binding for half-life extension.

• Understanding how pharmacokinetics, dosing strategies, and molecular distribution dictate the success or failure of ADCs in the clinic.
• Using computational simulations and high-resolution imaging to track molecular distribution in real-time.
• Broadening payload options.

ADCs have transformed the therapeutic landscape of oncology and have the potential to shift the treatment paradigm for immune and inflammatory (I&I) diseases by enabling the targeted delivery of payloads to disease-driving immune or inflammatory cells. Hummingbird Bioscience's platform & technologies engineers next-generation ADCs that have the promise to address key limitations of current I&I therapies for patients, including: efficacy ceiling, durability, and tolerability.

Dysregulation of inhibitory receptor function contributes to inflammatory diseases, and inhibitory checkpoint receptors, such as PD-1 and FcγRIIb, help restore immune homeostasis. S-4321 is a novel bifunctional agonist that selectively binds to and signals through the inhibitory receptors PD-1 on T cells and FcγRIIb on B cells and antigen presenting cells at the immune synapse. Unlike first generation of PD-1 depleting antibodies, S-4321 maintains PD-1 expression on T cells, avoids proinflammatory cytokine induction, does not deplete PD-1+ Tregs and promotes differentiation into effector Treg optimized for suppression and tissue homeostasis. By combining PD-1 agonism with selective engagement and agonism of FcγRIIb, S-4321 has the potential to restore immune homeostasis in cell-mediated autoimmunity. S-4321 is entering a Phase 1b basket study.

AMDC (Antibody Mimetics Drug Conjugate) is a novel multi-component therapeutic platform developed by our research group that utilizes the extremely high-affinity non-covalent interaction between genetically modified, low-immunogenic streptavidin and a bis-iminobiotin payload. With this system, a target-binding protein module-comprising a fusion of low-immunogenic streptavidin and an antibody mimetic-can be rapidly assembled simply by mixing it with a bis-iminobiotin-conjugated payload module, enabling the flexible construction of multifunctional therapeutics. The AMDC platform has already achieved proof of concept (POC) in multiple therapeutic modalities, including radionuclide therapy and photoactivated therapy.
　　In this presentation, we will discuss the development of an AMDC formulation named “Duo-HER2” that targets HER2-positive solid tumors. Duo-HER2 consists of a HER2-targeting VHH mimetic fused to low-immunogenic streptavidin and a bis-iminobiotin payload conjugated to duocarmycin, a highly potent DNA-alkylating cytotoxic agent capable of inducing cancer cell death at extremely low concentrations. Our research aims to establish practical development strategies for next-generation multifunctional biopharmaceuticals and to accelerate the clinical application of AMDC therapeutics for advanced cancer, a condition with extremely high unmet medical needs.

Neonatal Fc receptor is a popular target for treatment of autoimmune disorders due to its role in maintaining IgG levels. Development of next-generation FcRn blockers with improved pharmacodynamic effects and reduced frequency of dosing could be highly beneficial for patient quality of life and patient satisfaction. To achieve this, we generated and optimized Fc-ABDEGs equipped with albumin binding VHHs. Step-wise engineering was applied to optimize the position and number of VHHs, their affinity to albumin, and the linker connecting it to Fc-ABDEG. Novel FcRn-based cellular assays and human FcRn transgenic mice will also be addressed.

Antibody-based biologics continue to broaden the therapeutic landscape, and tailoring of effector functions and plasma half-life is a commercially competitive differentiator. In humans, the plasma half-life of most IgG antibodies but also albumin is about 3 weeks at average. This has made IgG the natural choice for design of antibody formats, while albumin is increasingly used as a fusion partner for a range of therapeutic modalities. Remarkably, the plasma half-life of these unrelated proteins is prolonged by a common cellular Fc receptor, FcRn. In addition, Fc engineering for enhanced or silenced effector functions is the key to secure potent and specific mode of actions, which must be carefully controlled on a case-to-case basis dependent on the context. In this talk, I will elaborate on how in-depth insights into the complex structural and cellular mechanisms that govern the functions of FcRn can pave the way for design of antibody and albumin based formats with improved binding and transport properties. This perspective will further be discussed in light of engineering for specific engagement of Fc receptors and the complement system.

• Costimulatory target selection: considerations around disease indication, tumor antigen, antibody format, and clinical strategy
• Engager optimization via sequence-based discovery paired with functional and developability assessments across mono- and bispecific formats
• Preclinical development of RNDO-564, a CD28 × Nectin-4 bispecific antibody in a Phase I clinical trial for Nectin-4-expressing solid tumors

The development of effective anti-fibrotic biotherapeutics is limited by a lack of human-relevant analytical frameworks linking immune modulation to functional tissue outcomes. Here, we present an immune-competent, human iPSC-based analytical platform that quantitatively resolves macrophage-fibroblast crosstalk in cardiac fibrosis. By integrating high-resolution spectral flow cytometry with functional co-culture and conditioned media assays, we define macrophage phenotypic states and directly map these states to cardiac fibroblast activation and extracellular matrix responses. This platform enables mechanism-linked potency and differentiation assessment of macrophage-targeting antibodies, supporting target validation, candidate ranking, and potency assessment for next-generation anti-fibrotic biologics.

Myeloid cells express several types of IgG Fc receptors, some mostly on the surface, others intracellularly. This includes the Fc gamma receptor (FcγR) family that mediates cellular effector functions upon receptor cross-linking on the cell surface by IgG immune complexes (IC). The neonatal Fc receptor (FcRn) is almost exclusively expressed in intracellular vesicles and is known for facilitating the long half-life and transcellular transport of IgG. Recent evidence suggests cooperative mechanisms between FcγRs and FcRn exist in the context of myeloid cell activation upon IgG IC binding and processing of IgG-opsonized targets. We found that FcγRs are required for efficient internalization of monomeric IgG into monocytic cells and IgG delivery to FcRn rather than random pinocytosis. We show how to exploit this cooperative mechanism between the two Fc receptor systems to improve delivery of engineered Fc-based therapeutics to FcRn in vitro and in vivo and propose how the receptor systems have evolutionarily co-evolved to ensure efficient IgG rescue in FcγR-expressing cells.

• Evaluating the industry-wide shift back towards small molecules and ADCs as interest in CGTs wanes due to high clinical risk.
• Addressing that engineering capabilities (and AI) have advanced faster than our discovery of novel, high-value targets.
• Thoughts on the next 5 years of the industry, which avenue will lead to greatest success?
• How can cross-border collaboration expedite progress and approvals?