1. Clinical trial VB-C-02 (VB10.16, 3 mg, in combination with atezolizumab). Cancer indication: HPV16+ advanced, non-resectable cervical cancer.
The VB-C-02 trial is fully enrolled and reported positive interim efficacy and safety data on May 9, 2022. Interim results from 39 patients with a median follow up of 6 months showed durable responses with a high disease control rate in heavily pre-treated advanced cervical cancer patients. Interestingly, anti-tumor efficacy was observed in both PD-L1 positive and negative patients.
The trial enrolled patients having received multiple lines of prior systemic therapy in recurrent or metastatic setting. Analysis showed the most robust clinical benefit in patients treated with up to two prior lines of therapy and in patients with lower metastatic burden. A high Disease Control Rate (DCR) was observed across all patient groups. Strong HPV16-specific T cell responses were associated with the clinical responses.
2. Clinical trial VB-C-03 (VB10.16, 3 mg and 9 mg, in combination with pembrolizumab). Cancer indication: HPV16+ non-resectable, recurrent or metastatic squamous cell head and neck cancer
VB10.16 in combination with atezolizumab was found to be well-tolerated and showed a safety profile comparable to atezolizumab monotherapy. Nykode expects to report the final safety and efficacy analysis from the VB-C-02 trial covering the full treatment phase for all patients during the first half of 2023.
The encouraging clinical efficacy and favorable safety profile that was observed with VB10.16 has led Nykode to update the development strategy for VB10.16. The VB-C-04 trial in advanced cervical cancer will focus on patients who failed first line treatment including checkpoint inhibitor treatment. It is a single arm trial with registrational intent and will be conducted in the United States. The first patient is expected to be dosed in the fourth quarter of 2023.
Nykode is also planning to conduct an open-label, dose-finding, single arm Phase 1/2a trial (VB-C-03) of VB10.16 in combination with pembrolizumab in patients with first line HPV16-postive, recurrent or metastatic squamous cell head and neck cancer as described in Nykode’s announcement on December 6, 2022. Nykode expects to enroll patients in Europe during the first half of 2023.
3. VB10.NEO (exclusively licensed to Genentech)
a. A) Clinical trial VB-N-01. (VB10.NEO, 3 mg in combination with CPI). Cancer indications: Melanoma, non-small cell lung cancer (NSCLC), clear renal cell carcinoma, urothelial cancer or squamous cell carcinoma of the head and neck (SCCHN)
b. Clinical trial VB-N-02 (VB10.NEO, 3-9 mg dose escalation, in combination with atezolizumab). Cancer indications: Locally advanced and metastatic tumors covering more than ten indications
Nykode presented positive immunogenicity results from the VB-N-01 trial on October 26, 2022. VB10.NEO showed a T cell response in 100% of the patients, including expansion of novel T cells in 95% of the patients. The responses were broad with the majority of the encoded neoepitopes being immunogenic and inducing a functional and strong CD8 T cell response. Multiple vaccinations boosted the breadth and magnitude of the immune responses, and most T cell responses were maintained for at least one year. VB10.NEO was generally safe and well-tolerated in patients with solid tumors and well-tolerated in combination with other cancer treatments.
4. Clinical trial VB-D-01 (Open label, dose escalation trial investigating the two vaccine candidates). VB2129 and VB2210 (Pathogen: SARS-CoV-2)
a. VB10.2129 (RBD candidate) – 2nd generation vaccine addressing novel variants of concern VB10.2129 encodes for the receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2 Beta variant of concern, B1.351.
b. VB10.2210 (T cell candidate) – 3rd generation universal broadly protective T cell vaccine T cells appear central in maintaining the protection against severe disease and death across current variants of concern. Nykode aims to induce a broad T cell response against validated epitopes from multiple SARS-CoV-2 antigens. The aim is to induce long-lasting protective immunity across all population groups and across current and future variants.
Nykode presented positive interim data from the VB10.2210 trial-arm in September 2022. VB10.2210 was found to boost Spike-specific T cell responses and induced de novo T cell responses to conserved non-Spike antigens found across SARS-CoV-2 variants, generating broad and CD8 dominated T cell responses post vaccination. Nykode’s vaccine candidate was safe and well-tolerated at all three dose levels. Nykode plans to guide on the future development strategy during the first half of 2023.
5. Autoimmune disorders
Autoimmune disorders are caused by unwanted immunogenicity to self-antigens. Antigen-specific tolerization for the treatment of autoimmune diseases has the potential to suppress autoimmunity without compromising normal immune function.
Nykode’s platform is uniquely positioned to induce tolerogenic T cell responses through specific targeting of tolerizing antigen specific cells. Initial preclinical proof-of-concept studies with tolerizing vaccine constructs are encouraging. Nykode has demonstrated the ability to increase antigen specific T regulatory cells and to shift the cytokine balance towards an immune suppressive profile in mice models. Further validation of the concept is ongoing in preclinical models.
The Company plans to provide further preclinical data from the tolerance platform during
the third quarter of 2023.
6. 4th Module, novel vaccine formats
The 4th module platform allows Nykode to introduce additional new coding regions to the vaccine with the purpose of further boosting or directing the immune responses.
Nykode has demonstrated how the Vaccibody™ molecule can be co-expressed with various immune-modulatory polypeptides. Compared to the Vaccibody molecule alone, the simultaneous expression of selected immune stimulatory cytokines was shown to boost the overall immune response of cancer vaccines and to stimulate an enhanced anti-tumor immune response in preclinical models. Similar, 4th module cytokines have also been demonstrated to boost T cell and antibody responses induced by a SARS-CoV-2 subunit vaccine in preclinical models. An additional 5th and 6th module may be added to even further boost and/or direct the immune responses. Nykode continues to explore the potential of additional immune modulatory polypeptides and combinations of these.
7. Other
On December 19, 2022, Nykode announced a strategic manufacturing partnership with Richter-Helm BioLogics GmbH & Co KG. Richter-Helm BioLogics will supply plasmid DNA for Nykode’s wholly owned and partnered product portfolio, providing the long-term expertise and capacity needed to support Nykode’s growth and pipeline development.
Nykode Quarterly Report Document Q4
