[Edaily Reporter Kim Saemi] #Y-Biologics is aiming for early-stage technology transfer in the preclinical phase, leveraging its proprietary trivalent antibody.
Y-Biologics is shifting its focus from an antibody platform company that has built a track record in joint R&D and technology transfers to a developer of proprietary multi-antibody new drugs. At the center of this shift is the multi-antibody-cytokine fusion platform “Multi-AbKine.”

"The 'Next Keytruda' Will Be Found in Bispecific and Multispecific Antibodies"

Yoon Joo-han, Head of Research at Y-Biologics, met with Edaily on the 28th in Yeongdeungpo-gu, Seoul, and stated, “The global antibody-based anticancer drug market is moving toward finding

the ‘

Next

Keytruda,’”

adding, “Bispecific and multispecific antibodies, which control multiple stages simultaneously, are now the mainstream.”

Director Yoon graduated from the Department of Genetic Engineering at Korea University, earned a master’s degree in Molecular Biology and Immunology from the same university’s graduate school, and obtained a Ph.D. in Immunology from the Mayo Clinic in the United States. He subsequently served as a postdoctoral researcher at Harvard Medical School and Boston Children’s Hospital, worked at the C&C New Drug Research Institute of JW Pharmaceutical, and held positions at several biotech startups before joining Y-Biologics as Director of Research in 2024.

Multi-Abca is a multi-specific immunocytokine platform that combines engineered cytokines, such as IL-2 variants, with bispecific or multispecific antibodies. While existing PD-1 antibodies and PD-1-based bispecific antibodies have focused on immune checkpoint blockade and regulation of the tumor microenvironment, MultiAppCain takes a different approach by adding cytokine signaling to selectively activate and proliferate T cells that attack tumors.

Director Yoon pointed out that while existing PD-1 immune checkpoint inhibitors have opened a new paradigm of long-term survival, their limitations include a limited number of responding patients and the continued presence of many non-responders and resistant patients.

He stated, “There are aspects where PD-1 alone is not enough, and VEGF alone is not enough either,” adding, “When we combined the two, we observed improved anticancer efficacy, which is why global big pharma companies have acquired PD-1×VEGF bispecific antibodies on a large scale.” He added, “The key difference with Y-Biologics is that we have attached an IL-2 variant to this, which activates T cells capable of responding to tumors.”

The presence of bispecific and multispecific antibodies is also growing in the global technology transfer market. Looking solely at the bispecific antibody sector, technology transfers totaling approximately 40 trillion won were completed between May and December of last year, involving deals such as Pfizer-3SBio, BMS-BioNTech, and Takeda-Innovent. This indicates that major deals in anti-cancer drug technology transfers are expanding beyond antibody-drug conjugates (ADCs) to include “next Keytruda” candidates such as PD-1×VEGF, PD-1×cytokine, and PD-1-based multispecific antibodies.

Lee Kyung-ho, Chief Financial Officer (CFO) of Y-Biologics, stated, “The company’s exploration of early-stage technology transfers for its preclinical multi-antibody candidates is also aligned with this global deal trend.” He emphasized, “Looking at recent global deals involving bispecific and multispecific antibodies, we are seeing many major deals emerging even at the early stages,” adding, “Given this trend, I believe there is a possibility of early technology transfer for AR170 and AR166 as well.”

Triple-antibody strategy… What sets AR170 and AR166 apart?

Y-Biologics’ flagship pipeline, AR170, is a PD-1×VEGF×IL-2v triple-antibody that combines a PD-1×VEGF bispecific antibody with an IL-2 variant. Research Institute Director Yoon noted, “There are issues with PD-1×VEGF bispecific antibodies, and the PD-1×IL-2 class also has its limitations,” adding, “We started with the idea of attaching our IL-2 to the PD-1×VEGF bispecific antibody.”

AR170 is designed to simultaneously enhance immune checkpoint blockade and T-cell activation by utilizing VEGF in the tumor microenvironment. Director Yoon explained, “In environments rich in VEGF, AR170 acts more potently, significantly enhancing PD-1/PD-L1 blockade.” He continued, “By binding to PD-1-expressing immune cells while simultaneously delivering an IL-2 signal, T cells capable of fighting tumors proliferate and effectively attack the tumor.”

According to the data he released, in the presence of VEGF, AR170’s PD-1 binding increased 44-fold, and its PD-1/PD-L1 blocking function increased 27-fold. IL-2 signaling was also enhanced by approximately 3.7-fold. Director Yoon stated, “We observed excellent results in mouse experiments,” adding, “While a representative competitive compound for PD-1×VEGF initially controlled tumor growth but later allowed it to resume, AR170 maintained tumor control for a much longer period at the same dosage.” However, AR170 is still in the preclinical stage.

Another candidate compound, AR166, features a PD-1×LAG3×IL-2v structure. Director Yoon explained, “We had been developing the LAG3 antibody as a standalone candidate for a long time, but we determined it lacked competitiveness because its efficacy was not significant on its own.” He continued, “We revisited this compound, transformed it into a bispecific antibody targeting PD-1, and attached IL-2 to it, giving it a new form.” He elaborated, “The basic concept is to block both PD-1 and LAG3 while simultaneously delivering an IL-2 signal to amplify the soldiers fighting the tumor.”

AR169 is a confidential pipeline for which specific targets have not yet been disclosed. Director Yoon remarked, “We are adding something to PD-1,” noting that it takes the form of a bispecific antibody targeting tumor-associated antigens (TAAs) with a cytokine attached. He added, “We are currently verifying the actual efficacy in patient samples through international collaborative research,” and hinted, “AR169 will likely be unveiled soon.”

Translational Research as the Key to Early Technology Transfer… Data to Be Released at SITC

Y-Biologics regards translational research as the core basis for early technology transfer. Director Yoon pointed out, “When asked what Big Pharma looks for before clinical trials, they place great importance on translational research data,” adding, “It is crucial to evaluate whether immune cells in actual patient samples are activated by our compound, rather than relying solely on animal experiments.”

Y-Biologics is building a collaborative network for translational research with major domestic hospitals. Research on AR170 is currently underway, focusing on samples from medical staff and colorectal cancer patients, while the AR166 project involves translational research teams specializing in colorectal and lung cancers. AR169 is undergoing patient sample-based validation through international joint research with overseas research institutions. The company has also established a new translational research team at its Munjeong Lab in Seoul to compile data packages for technology transfer, focusing on anti-tumor efficacy and molecular mechanisms based on patient-derived cancer tissue samples.

The company views this year’s Bio USA and the Society for Immunotherapy of Cancer (SITC) conferences as pivotal events. Research Institute Director Yoon stated, “We plan to have more in-depth discussions with big pharma companies at Bio USA next month.” Y-Biologics plans to present ex vivo translational research data at SITC in November and finalize technology transfer discussions. Preclinical studies for AR170 and AR166 are currently underway, with the goal of submitting an Investigational New Drug (IND) application next year.