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Technology

Multi-Abkine

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Multi-AbKine (Multi-Antibody-Cytokine Fusion Protein)

• Global first-in-class/best-in-class next-generation immuno-oncology platform

• Completion of global Phase 1/2a trial confirming safety and efficacy of Y-Biologics’ anti–PD-1 acrixolimab-based bispecific antibody, designed to activate immunity and amplify cytokine responses

• Incorporation of conditional cytokine activators that function only upon PD-1 binding, optimizing both efficacy and safety

• Conventional monoclonal antibodies are designed to recognize only a single antigen.

• In contrast, bispecific antibodies, which lead the antibody therapeutics field today, can simultaneously recognized two different antigens that enable synergistic therapeutic effects.

• Y-Biologics’ Multi-AbKine employs an innovative multispecific platform that allows for dual-targeting via bispecific antibodies, followed by cytokine-mediated activation and proliferation of anti-tumor immune cells.

(Left) When PD-1 is targeted solely by a monoclonal antibody, it blocks the interaction between PD-1 on T cells and PD-L1 on tumor cells, allowing T cells to attack the tumor. However, molecules like VEGF, which promote immune cell proliferation and tumor progression, remain active. As a result, the tumor continues to grow, and persistent activity causes T cell exhaustion, ultimately limiting anti-tumor effects.

(Center) Bispecific antibodies that block both PD-1 and VEGF can bind VEGF and reduce immune cell proliferation and signaling in the tumor microenvironment. However, T cell exhaustion is not prevented allowing tumors to regrow.

(Right) Multi-AbKine, by fusing cytokines with bispecific antibodies, overcomes these limitations through a triple-action mechanism. It promotes proliferation of anti-tumor T cells and sustains long-term anti-tumor effects by also enhancing memory T cell function.

(Top) When PD-1 is targeted solely by a monoclonal antibody, it blocks the interaction between PD-1 on T cells and PD-L1 on tumor cells, allowing T cells to attack the tumor. However, molecules like VEGF, which promote immune cell proliferation and tumor progression, remain active. As a result, the tumor continues to grow, and persistent activity causes T cell exhaustion, ultimately limiting anti-tumor effects.

(Center) Bispecific antibodies that block both PD-1 and VEGF can bind VEGF and reduce immune cell proliferation and signaling in the tumor microenvironment. However, T cell exhaustion is not prevented allowing tumors to regrow.

(Bottom) Multi-AbKine, by fusing cytokines with bispecific antibodies, overcomes these limitations through a triple-action mechanism. It promotes proliferation of anti-tumor T cells and sustains long-term anti-tumor effects by also enhancing memory T cell function.

Superior Central Killing and Immune Cell Proliferation Function of Multi-AbKine

• Tumor cell killing of our leading Multi-AbKine pipeline was compared to that of a PD-1 immune checkpoint inhibitor

• After co-culturing PBMCs from healthy donors with NSCLC (HCC827) tumor cells, PD-1 inhibitor (pembrolizumab) and Multi-AbKine were separately applied. Tumor cell death and immune cell proliferation over time were analyzed and compared using the Incucyte® Live-Cell Analysis system. (Green: tumor cells, Red: immune cells)

PD-1 inhibitor treatment

PD-1 inhibitor treatment

PD-1 inhibitor treatment

Cancer cell survival

Cancer cell survival

Cancer cell survival

Multi-AbKine treatment

Multi-AbKine treatment

Complete elimination of cancer cells

Complete elimination of cancer cells

Complete elimination of cancer cells

Cancer cells

Cancer cells

Immune cells (T cells)

Immune cells (T cells)

Multi-AbKine treatment

• As shown in the video, while many tumor cells (green) remain after treatment with a PD-1 inhibitor, treatment with Multi-AbKine results in complete tumor cell (green) death and a significant increase in immune cells (red).