Cancer

VTP-850: A next-generation immunotherapeutic candidate for prostate cancer

Unmet need

Prostate cancer is the second most frequent cancer diagnosis in men and the fourth most common cancer overall worldwide.[1] In 2020, approximately 1.4 million new cases were diagnosed, and approximately 375,300 deaths occurred.[1] The incidence of prostate cancer is expected to increase due to longer life expectancy and lifestyle factors. Some prostate cancer patients can be treated with local therapy including surgery (e.g. prostatectomy) or targeted radiation. However, 20-30% of patients who receive local therapy continue to experience rising levels of Prostate Specific Antigen (PSA) which indicates that the disease has not been not cured by local therapy.[2] Additional options for those patients who experience this biochemical recurrence include systemic therapies such as hormonal or chemotherapy, which could have associated toxicity and side effects.[3]

Our approach

Barinthus Biotherapeutics is developing VTP-850, a sequential combination immunotherapeutic consisting of an initial dose using the ChAdOx platform and further doses(s) using MVA encoding multiple prostate cancer associated antigens including 5T4 (encoded in VTP-800). Using VTP-850 as a monotherapy in prostate cancer patients who have received local therapy and are experiencing a biochemical recurrence may provide therapeutic benefits to those patients and avoid other systemic therapies.

Development status

VTP-850 builds on the positive data from a Phase 1/2a clinical trial of VTP-800, our first-generation product candidate which encoded 5T4, an antigen expressed by most prostate cancers. VTP-800 was administered to patients with prostate cancer in two clinical trials sponsored by the University of Oxford. VTP-850 is our next-generation immunotherapeutic which encodes for multiple prostate-associated antigens including PSA. PAP, STEAP1 and 5T4 and is due to enter a Phase 1 clinical study in Q1 2023.
Preclinical and clinical data from our first-generation prostate cancer immunotherapy, VTP-800, have informed the development of VTP-850 as it contains the same 5T4 antigen encoded in VTP-850.

• In a Phase 1 study of VTP-800, VANCE01, it was observed that 59% of participants had no detectable T cell response at baseline and developed a new 5T4-specific T cell response, as measured by an ex vivo gamma interferon ELISpot. T cell infiltration into the resected prostate was also observed. This data was presented at ASCO 2018.
• ADVANCE was an open label, non-randomized Phase 1/2 clinical trial of VTP-800 in combination with anti-PD-1 checkpoint inhibitor, nivolumab, in 23 patients with metastatic prostate cancer. The trial was sponsored by the University of Oxford.
• In the 23 mCRPC patients who received VTP-800 in conjunction with an anti-PD-1, 5 patients (22%) had a >50% reduction in PSA level at any timepoint compared to baseline (median of 88 ng/ml). Three of eight patients with measurable disease had partial tumor responses.

Key references

• Cappuccini, F., et al. 2020. Safety and immunogenicity of novel 5T4 viral vectored vaccination regimens in early stage prostate cancer: a phase I clinical trial. Journal for ImmunoTherapy of Cancer, 8(1)
• Cappuccini, F., et al. 2016. Immunogenicity and efficacy of the novel cancer vaccine based on simian adenovirus and MVA vectors alone and in combination with PD-1 mAb in a mouse model of prostate cancer. Cancer immunology, immunotherapy, 65(6), pp.701-713.
• Cappuccini, F., Pollock, E., Stribbling, S., Hill, A.V. and Redchenko, I., 2017. 5T4 oncofoetal glycoprotein: an old target for a novel prostate cancer immunotherapy. Oncotarget, 8(29), p.47474.
• Redchenko, I., et al. 2018, June. VANCE: First-in-human phase I study of a novel ChAdOx1-MVA 5T4 vaccine in low and intermediate risk prostate cancer. American Society of Clinical Oncology.

Clinical trial references

VANCE – NCT02390063 (ClinicalTrials.gov)

ADVANCE – NCT03815942 (ClinicalTrials.gov)

PCA001 – NCT05617040 (ClinicalTrials.gov)

VTP-1100

Unmet Need

Over 600,000 patients are affected with HPV-associated cancer annually, resulting in more than 342,000 deaths in 2020.[4] 70% of those cases being attributed to HPV types 16 and 18 with well validated antigenic targets.[4] In these HPV-associated cancers, such as head & neck and cervical, checkpoint inhibitors can have a low response rate.[5]

Our Approach

VTP-1100 is a sequential combination immunotherapeutic candidate with SNAP and ChAdOx components encoding HPV16 antigens. HPV16 antigens are fully foreign, which results in a high affinity T cell response.

Development status

In HPV cancer preclinical models, SNAP inhibited tumor growth alone and in combination with checkpoint inhibitors. Preclinical models evaluating sequential combination of SNAP and ChAdOx showed a significant increase in the quantity of antigen-specific T cells compared to either platform given alone.