Kyowa Kirin (4151) Corporate presentation summary

Bispecific antibody rationale

• Conventional monospecific antibodies face efficacy limits from single-antigen targeting, resistance and multiple factors; target selectivity and toxicity are additional constraints.

• Clinical trials of multispecific antibodies surged over the past decade.

• T-cell engagers dominate marketed multispecific products; immune modulation is the largest pipeline category, TCE remains central, and dual blockade is expanding.

REGULGENT M design and manufacturing

• A common light chain with natural IgG sequences prevents unwanted heavy/light-chain pairings and supports a uniform, low-immunogenicity structure.

• N- and C-terminal bivalent formats offer IgG-like properties and kinetics, diverse mechanisms of action, and compatibility with conventional antibody processes.

• One heavy-chain type and one light-chain type yield a single pairing, addressing mispairing-related impurities, lower production volume, purification inefficiency, cost and technical hurdles.

• The approach was inspired by human antibody-producing animals and the observation that antibodies to different targets can share the same light chain.

Applications and development examples

• The platform is positioned to enable previously undruggable toxic targets and mimic complex-forming ligands, supporting drug concepts designed to activate signals selectively.

• TRAIL-R2 induces apoptosis; prior TRAIL-R2 drugs entered clinical trials but were discontinued for insufficient efficacy or liver toxicity, prompting a need for strong cancer-cell-specific death signals.

• In the PSMA/TRAIL-R2 bispecific, the PSMA arm targets cancer cells and the TRAIL-R2 arm triggers cell death.

• REGULGENT M productivity was described as comparable to IgG in transient and stable CHO expression work.

• KK2260 blocks cellular iron uptake only when binding cancer antigens, with regression of patient-derived tumors in mice; KK2269 activates anti-tumor immune cells only with cancer-antigen binding, with implanted tumors regressing.

• The technology is broadly deployable and in clinical trials; discovery priorities include patient needs, meaningful efficacy and safety, real-world deliverability, learning from outcomes and a sustainable platform.