PD-1 x VEGF and PD-L1 x VEGF bispecific antibodies: a business, pipeline and competitor analysis from an industry perspective

PD-1 x VEGF and PD-L1 x VEGF bispecific antibodies: a business, pipeline and competitor analysis from an industry perspective

This report provides you with a landscape description and analysis of PD-1 x VEGF and PD-L1 x VEGF bispecific antibodies regarding stakeholders, R&D pipeline, clinical profile and molecular structure of drug candidates and business deals from an industry perspective as of February 2025. The first-in-class and so far best-in-class PD-1xVEGF bispecific antibody ivonescimab has set the bar for competitors in the pipeline for a superior clinical profile compared with anti-PD-1 pembrolizumab (Keytruda) and for economic terms of the licensing agreement. The simultaneous blockade of PD-1 and VEGF (”cooperativity”) by one molecule may produce enhanced antitumor activity with an improved safety profile compared with the co-administration of separate anti–PD-(L)1 and anti-VEGF therapies. A next generation of trispecific PD-(L)xVEGF antibodies with a third specificity may even further improve the clinical benefit. Nearly all of the PD-(L)1xVEGF antibody development candidates in the pipeline originate from Chinese biotechnology companies with focus on development in China. This provides an opportunity for Western biopharmaceutical companies for strategic collaborations in global development and marketing.

The report brings you up-to-date with information about and analysis of:

• R&D pipeline of bispecific and trispecific PD-1xVEGF(R) and PD-L1xVEGF antibodies;
• Molecular structure of PD-(L)1xVEGF(R) antibodies in development;
• Preclinical and clinical profile of PD-(L)1xVEGF(R) antibodies;
• Cancer indications in early development and in global development;
• Clinical experience with PD-(L)1xVEGF antibodies;
• Background profile of stakeholders (originator and licensee companies);
• Competitor analysis;
• Established market size for PD-1 and PD-L1 checkpoint inhibitor antibodies;
• Business deals with economic terms: spin-offs, financing, licensing; mergers & acquisitions, company valuation.

In preclinical studies, anti-vascular endothelial growth factor (VEGF) and anti–PD-(L)1 antibodies were found to have synergistic antitumor activity. Anti-VEGF not only inhibits angiogenesis but also increases immune effector cell trafficking and infiltration into the tumor microenvironment, allowing for an immuno-responsive environment, which leads to enhanced efficacy of anti–PD-(L)1 inhibitors. Combining anti–PD-(L)1 antibodies with antiangiogenic agents was found to have antitumor activity and tolerable safety in advanced solid tumors. Clinical studies have shown that the combination of PD-(L)1 and VEGF antibodies significantly improves clinical benefit over PD-(L)1 antibody alone in certain settings.

To combine both targeting approaches, bispecific antibodies targeting PD-1 and VEGF by one molecule have been designed and preclinical studies showed that the combination in one molecule was superior to the combination of two separate molecules in antitumor activity.

As PD-1 and VEGF co-express in the tumor microenvironment, the dual-target design of a bispecific antibody combines PD-1 and VEGF to enable the enrichment and retention of macromolecular drugs in the tumor microenvironment, leading to a reduced distribution in the peripheral blood and a decreased toxicity caused by off-target effects.

Methodology:

This report evaluates the industry landscape of PD-1xVEGF(R) and PD-L1xVEGF bispecific and trispecific antibodies in research and development. The report provides a comprehensive overview of the R&D and partnering activities of pharmaceutical and technology companies in the field of PD-(L)1xVEGF(R) antibodies. This report is based on the identification and description of corporate stakeholders including biopharmaceutical companies and biotechnology companies. All publicly available information is fully referenced, either with scientific references (abstracts, posters, presentations, full paper) or hyperlinks leading to the source of information, such as press releases, corporate presentations, annual reports, SEC disclosures and homepage content.

Who will benefit from the report?

• Business development and licensing (BDL) specialists;
• Venture capital, private equity and investment managers;
• Managers of Big Pharma venture capital firms;
• Financial analysts;
• CEO, COO and managing directors;
• Corporate strategy analysts and managers;
• Chief Technology Officer;
• R&D Portfolio, Technology and Strategy Management;
• Clinical and preclinical development specialists.