Blocking Two Tumour Escape Routes at Once Akeso’s Anti-PD-1/VEGFA Bifunctional Antibody VP101

Tumours evade immune attack and sustain their growth through multiple mechanisms simultaneously. A divisional patent from Chinese biopharmaceutical company Akeso Biopharma describes VP101, a bifunctional antibody that blocks both the PD-1/PD-L1 immune checkpoint axis (which suppresses T-cell activity) and the VEGFA/VEGFR2 angiogenesis pathway (which supplies tumours with new blood vessels) in a single molecule.

The Problem

Cancer treatment by immune checkpoint inhibition has been one of the most significant advances in oncology of the past decade. Antibodies targeting the PD-1/PD-L1 pathway have demonstrated durable responses across a wide range of tumour types, including non-small cell lung cancer, melanoma, renal cell carcinoma, and lymphoma, by releasing tumour-infiltrating T cells from the immunosuppression enforced by PD-L1-expressing tumour cells.

However, monotherapy with checkpoint inhibitors does not work for all patients, and tumours can develop resistance. One major mechanism by which tumours sustain growth even in the presence of immune pressure is angiogenesis: the formation of new blood vessels that supply the tumour with nutrients and oxygen. Vascular Endothelial Growth Factor A (VEGFA) is the primary driver of tumour angiogenesis, acting through VEGFR2 to stimulate endothelial cell proliferation, migration, and new vessel formation. The VEGF pathway also contributes to an immunosuppressive tumour microenvironment by impairing the function and trafficking of anti-tumour immune cells.

Anti-VEGFA antibodies such as bevacizumab (Avastin) are approved for multiple tumour types, but their use as monotherapy is limited. The combination of checkpoint inhibition with anti-angiogenic therapy has shown clinical promise, but combining two separate antibody drugs adds complexity, cost, and potential for combined toxicity. A single bifunctional molecule that can achieve both mechanisms simultaneously from a single pharmacological agent would be preferable.

What This Invention Does

VP101 is a humanised bifunctional antibody comprising two protein functional regions in a single molecule. The first functional region targets VEGFA, with heavy chain variable region CDRs 1-3 having amino acid sequences set forth in SEQ ID No. 15-17 and light chain variable region CDRs 1-3 with sequences from SEQ ID No. 18-20. The second functional region targets PD-1, with heavy chain CDRs 1-3 from SEQ ID No. 21-23 and light chain CDRs from the corresponding sequences.

The antibody is constructed in an IgG-scFv (Morrison) format, with one arm providing the conventional IgG antibody structure for VEGFA binding and the scFv (single-chain variable fragment) appended to provide PD-1 binding. This format resembles a natural IgG antibody in structure, which confers advantages in stability, expression yield, and Fc-mediated effector functions.

VP101 has been shown to simultaneously bind to VEGFA and PD-1, block the VEGFA-VEGFR2 interaction (inhibiting angiogenesis), block the PD-1/PD-L1 interaction (relieving immunosuppression), promote secretion of IFN-gamma and IL-2 by immune cells, and inhibit VEGFA-induced proliferation of vascular endothelial cells. Preclinical data shows potential utility in liver cancer, lung cancer, melanoma, renal tumour, ovarian cancer, and lymphoma.

Key Features

Dual target blockade. A single antibody molecule simultaneously binds to both VEGFA and PD-1, blocking two distinct tumour survival pathways – angiogenesis and immune checkpoint evasion – from one pharmacological agent.

IgG-scFv (Morrison) format. The bifunctional design uses a conventional IgG structure for one antigen-binding arm and an scFv fusion for the second, approximating natural IgG architecture for stability, expression efficiency, and Fc-mediated functions.

Anti-VEGFA arm. Derived from bevacizumab-related variable region sequences, the VEGFA-binding arm blocks VEGFA from binding to VEGFR2, inhibiting the angiogenesis signalling pathway that supplies tumours with blood vessels.

Anti-PD-1 arm. Based on the 14C12H1L1 humanised anti-PD-1 antibody developed previously by the inventors, the PD-1-binding arm blocks PD-L1 from binding to PD-1 on T cells, relieving immune checkpoint suppression and enhancing T-cell-mediated tumour killing.

Enhanced cytokine secretion. The bifunctional antibody promotes secretion of IFN-gamma and IL-2 by human immune cells, markers of effective anti-tumour T-cell activation.

Who Is Behind It?

The applicant is biopharmaceutical company Akeso Biopharma, Inc. of China. The named inventors are Li Baiyong, Zhang Peng, Wang Zhongmin Maxwell, and Xia Yu. The work builds on prior Chinese patent CN106977602A for the anti-PD-1 antibody 14C12H1L1. This divisional was filed on 26 February 2026, derived from parent application AU 2019332708, which traces to PCT/CN2019/103618 with Chinese priority from application 201811025484 filed 30 August 2018. Spruson and Ferguson in Sydney are the Australian patent attorneys.

Why It Matters

The combination of checkpoint inhibition with anti-angiogenic therapy has been validated in multiple clinical contexts, with combinations of PD-1 inhibitors and bevacizumab approved by regulatory agencies for liver cancer, non-small cell lung cancer, and other tumour types. However, the use of two separate monoclonal antibodies raises coordination challenges around dosing schedules, independent pharmacokinetics, and additive manufacturing costs.

A bifunctional antibody that achieves both mechanisms through a single molecule with unified pharmacokinetics simplifies dosing, potentially improves the stoichiometric relationship between the two mechanisms at the tumour site, and may enable more predictable combination therapy. Akeso’s development of VP101 – which has advanced to clinical investigation as an anti-cancer bispecific – demonstrates the translational potential of this dual-targeting approach.

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AU 2026201467 was published in the Australian Official Journal of Patents on 19 March 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.

Related Concepts

Immune checkpoint inhibition and anti-angiogenic therapy are two of oncology’s most important treatment strategies. Checkpoint inhibitors release tumour-infiltrating T cells from suppression, while anti-VEGF agents such as bevacizumab cut off the tumour’s blood supply. Bispecific antibodies that combine both mechanisms into a single molecule represent a compelling approach to overcoming tumour resistance with unified pharmacokinetics and potentially reduced treatment complexity.