Pipeline

VB10.16

Nykode’s wholly owned lead product candidate, VB10.16, is a DNA-based therapeutic vaccine targeting malignancies caused by the cancer-inducing Human Papillomavirus 16 (HPV16). HPV is responsible for more than 600,000 new...Nykode’s wholly owned lead product candidate, VB10.16, is a DNA-based therapeutic vaccine targeting malignancies caused by the cancer-inducing Human Papillomavirus 16 (HPV16). HPV is responsible for more than 600,000 new cancer cases worldwide annually, with HPV16 being the most predominant cause of disease. Cervical cancer is the fourth leading cause of cancer deaths in women, and HPV16 accounts for 50-60% of these cases. Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer type, with around 30% of HNSCC cases caused by HPV, and HPV16 being the most frequent type (REF de Martel C et al. Int J Cancer 2017). Besides cervical cancer and HNSCC, HPV16 infection can also lead to the development of anal/rectal, penile, vulvar, and vaginal cancers, with the incidence increasing in the last decade (REF Cheng-I L et al. JAMA Network Open 2022).

The Nykode VB10.16 clinical development program includes four different trials. VB-C-01 was a first-in-human trial in 34 women with high-grade cervical intraepithelial neoplasia. The trial is completed and showed that VB10.16 monotherapy was well tolerated and exhibited early signs of clinical efficacy. VB-C-02 was a Phase 2 trial in 52 women with advanced and recurrent cervical cancer, investigating the safety and efficacy of VB10.16 in combination with the immune checkpoint inhibitor atezolizumab. The trial is completed and showed that VB10.16 in combination with atezolizumab was well tolerated, with patients demonstrating a higher objective response rate and prolonged overall survival compared to the current standard of care based on data from historical controls. A subgroup analysis showed that this treatment effect was more pronounced in PD-L1 positive patients, particularly those who had only been treated with one prior line of systemic anticancer therapy.

The protocol for the VB-C-05 trial in locally advanced cervical cancer is currently being developed. It aims to incorporate VB10.16 into the existing treatment regimen of pembrolizumab with chemoradiotherapy, which recently received FDA approval. Nykode is also conducting a phase 1/2a trial to investigate the efficacy and safety of VB10.16 in combination with pembrolizumab in patients with unresectable, recurrent, or metastatic HPV16 positive and PD-L1 positive head and neck squamous cell carcinoma (HNSCC). The VB-C-03 trial is currently ongoing in Europe.

As part of a strategic repositioning in August 2024, it was decided to discontinue the VB-C-04 trial to focus the development on locally advanced cervical cancer and recurring metastatic head and neck cancer. The VB-C-04 trial was designed and initiated to investigate VB10.16 in combination with atezolizumab in patients with HPV16+ recurrent/metastatic cervical cancer who are refractory to pembrolizumab with chemotherapy with or without bevacizumab.

VB10.NEO

In a global collaboration with Genentech, Nykode develops individualized therapeutic cancer vaccines targeting tumor-specific antigens, called neoantigens, arising from somatic gene mutations in malignant cells during neoplastic transformation. Every patient’s...In a global collaboration with Genentech, Nykode develops individualized therapeutic cancer vaccines targeting tumor-specific antigens, called neoantigens, arising from somatic gene mutations in malignant cells during neoplastic transformation. Every patient’s tumor is unique, and to effectively address this challenge, the principle of individualized cancer treatments is emerging quickly as an important part of future therapeutic options. The investigational medicinal product (IMP), named VB10.NEO, is intended for use as a therapeutic vaccination in patients with locally advanced or metastatic solid tumors.

Nykode has developed a well-defined process to identify and select optimal neoepitopes specific to each patient’s tumor. The selected neoepitopes are combined and synthesized to generate the Neoepitope Antigenic Module, and the VB10.NEO drug product is manufactured using a standardized manufacturing process. This personalized medicine approach allows vaccination of each patient with a unique and optimized cancer vaccine to induce a cellular immune response specific to neoantigens expressed by each patient’s tumor.

In April 2023, the results of the VB N-01 trial were presented. The data showed that VB10.NEO was generally well tolerated in patients with various pre-treated and advanced tumor entities. VB10.NEO induced broad and long-lasting neoantigen-specific T cell responses, with the majority of the tested neoantigens activating polyfunctional CD8 T cells. The T-cell responses were elicited in both TMB (tumor mutational burden) high and low tumors, indicating the selection of high-quality neoepitopes within different tumor entities. Additionally, identical expanded T-cell clones were observed in the tumor and in the blood post-vaccination, providing proof-of-concept that vaccine-induced neoantigen-specific T cells in the periphery can infiltrate tumors.