Cancer

VTP-600: Immunotherapeutic candidate targeting MAGE-A3 and NY-ESO-1 Antigens

Strategic Collaboration with LUDWIG INSTITUTE FOR CANCER RESEARCH and CANCER RESEARCH UK

Unmet Need

Lung cancer is the most frequent cause of cancer death worldwide.[1] In 2020, approximately 2.2 million new cases were diagnosed and 1.8 million deaths occurred.[1] Approximately 84% of lung cancers are cases classified as Non-Small Cell Lung Cancer (NSCLC).[2] The most important histological distinction is squamous versus non-squamous, as it impacts selection of systemic therapy. About 25% to 30% of patients have tumors with squamous histology, which is associated with a worse prognosis and a worse response to chemotherapy.[3] Better combination approaches are needed in first-line standard-of-care setting to improve long-term outcomes for NSCLC patients.

Our Approach

VTP-600 is a sequential combination immunotherapeutic candidate with ChAdOx and MVA components encoding tumor-associated antigens MAGE-A3 and NY-ESO-1.

MAGE-A3 and NY-ESO-1 are believed to be important target antigens for NSCLC as well as other tumors. MAGE-A3 and NY-ESO-1 are cancer/testis antigens, which are frequently expressed on cancer cells but have limited expression in normal tissues. MAGE-A3 is expressed in 48% of squamous NSCLC and 24% of non-squamous NSCLC. NY-ESO-1 has been shown to have an expression rate of 27% across all NSCLC types.

Development status

Barinthus Biotherapeutics has established a joint initiative with the Ludwig Institute for Cancer research and VOLT, to progress the clinical development of VTP-600. VTP-600 entered the clinic in December 2021 as part of a Phase 1/2a trial sponsored by Cancer Research UK. NSCLC patients are randomised to receive either VTP-600 in combination with standard of care (chemotherapy and anti-PD-1, pembrolizumab), or standard of care.

Key references

• Chen, X., et al. 2017. Expression and prognostic relevance of MAGE-A3 and MAGE-C2 in non-small cell lung cancer. Oncology letters, 13(3), pp.1609-1618.
• Näslund, T.I., et al. 2007. Comparative prime-boost vaccinations using Semliki Forest virus, adenovirus, and ALVAC vectors demonstrate differences in the generation of a protective central memory CTL response against the P815 tumor. The Journal of Immunology, 178(11), pp.6761-6769.
• Coulie, P.G., Van den Eynde, B.J., Van Der Bruggen, P. and Boon, T., 2014. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nature Reviews Cancer, 14(2), p.135.
• Romero, P., et al. 2016. The Human Vaccines Project: A roadmap for cancer vaccine development. Science Translational Medicine, 8(334), pp.334ps9-334ps9.