March 25, 2019 POSITIVE 12-MONTH RESULTS FROM PHASE IIa CLINICAL STUDY IN HIGH GRADE CERVICAL DYSPLASIA PROVIDES PROOF-OF-CONCEPT FOR VACCIBODY’S IMMUNOTHERAPY PLATFORM AND LEAD CANDIDATE VB1O.16
Oslo, March 25, 2019 Vaccibody AS today announced positive 12-month results from the phase IIa part of the clinical study VB C-01. This study is a first human dose, open-label, multicenter phase I/IIa study of VB10.16 immunotherapy for the treatment of high grade Cervical Intraepithelial Neoplasia (CIN 2/3) caused by human papillomavirus 16 (HPV16). The primary objective of the study was to evaluate the safety and tolerability of VB10.16. The secondary objectives were to assess T cell mediated immune responses in the peripheral blood and to evaluate early signs of efficacy by means of CIN regression and HPV clearance. The vaccine was delivered with a PharmaJet® Stratis Needle-free Injection System.
The phase 1 part of the trial has previously been reported. It was completed in 2017 and showed that VB10.16 was well tolerated with no clinical important safety signal, the optimal vaccine schedule was identified (week 0, 3, 6) and suggested adding a fourth vaccination to maintain the strong immunogenic response.
The phase 2a study enrolled 18 CIN2/CIN3 patients, 1 patient was not HPV16 positive and thus 17 patients received four doses of 3 mg VB10.16 at week 0, 3, 6 and 16. The treatment with the four doses of VB10.16 was well tolerated. No serious adverse advents (SAEs) or unexpected adverse events were reported. The most frequently reported AEs were transient mild to moderate reactions at the injection site.
Two patients had conization and one patient withdrew after 9 months and could not be assessed at 12 months visit. Of the remaining 14 patients 12 patients showed a reduction in the lesion size; 8 had more than a 50% reduction in lesion size. Presence of HPV16 was evaluated from immunohistochemistry (p16) and COBAS (Roche diagnostics), all patients had positive HPV16 at study entry and 8 of the 14 patients had negative HPV16 in one or both of the two tests at 12 months, indicating clearance of the HPV16 infection. Histopathological regression to low grade neoplasia (CIN1) or no disease was seen in 8 patients. Of the 6 patients that has not regressed to CIN1 or less at 12 months, 5 patients showed upregulation of PD-L1 in the lesions which may delay or inhibit elimination of all affected cells. Three of these patients had also persistent co-infection with other high-risk HPV strains, including one patient which had cleared HPV16.
Immunological analyses of the peripheral T cell responses demonstrated a strong HPV16-specific T cell immune response in 17 of 17 patients. The response was increased after vaccination in 16 of 17 patients against both HPV16 E6 and E7 antigens used in the vaccine. One patient had a strong baseline response and the response was not further increased.
These results constitute a proof-of-concept for VB10.16 and the Vaccibody DNA vaccine technology delivered by jet injection to induce rapid, strong and long-lasting immune responses which can lead to elimination of pre-malignant and malignant cells. Interestingly, the observed PD-L1 upregulation provides a strong rationale for moving VB10.16 into HPV16 positive cancer in combination with anti-PD-1/PD-L1 checkpoint inhibitor therapy.
Martin Bonde, CEO of Vaccibody, commented: We are very pleased with the 12-months results from the phase IIa clinical study in high grade cervical dysplasia. The data support what we have reported earlier and delivers a solid clinical proof-of-concept for Vaccibody’s immunotherapy platform and lead candidate VB10.16. The fact that we observe PD-L1 upregulation in response to vaccination in the patients that do not have CIN regression at 12 months, substantiates the mechanism of action of the vaccine and invites to pursue potential synergistic effects by combining therapeutic Vaccibody cancer vaccines and checkpoint inhibitors, like we have observed in preclinical experiments. We are therefore very excited about our newly entered collaboration with Roche to explore a combination of Vaccibody’s VB10.16 and the PD-L1-blocking immune-checkpoint inhibitor atezolizumab (Tecentriq®) in patients with advanced cervical cancer. Based on the above data Vaccibody plans to start a phase II study with up to 50 cervical cancer patients in the second half of 2019.
About cervical cancer
Cervical cancer is the most commonly occurring cancer among women in developing countries and is the second most commonly occurring cancer amongst women worldwide. An estimated 45,800 cases of cervical cancer will be diagnosed in the US and EU in 2019 and similarly an estimated 18,400 deaths from cervical cancer will occur in 2019. Cervical cancer is caused by high risk HPV. HPV16 is the type that most frequently causes cancer. It has been reported to be the most common genotype in high grade cervical intraepithelial neoplasia. It is detected in up to 60% of all cervical cancers, especially in younger women and it has also been found to play an essential role in the development of several other cancer types (approximately 90% of anal cancers; 40% of penile, vaginal, and vulvar cancers; 25% of oral cavity cancers and 35% of oropharyngeal cancers). Gardasil® and Cervarix® are preventive HPV vaccines which prevent infection of HPV, but these do not have an effect in already infected patients. A high percentage of the eligible population for the preventive vaccines does not get vaccinated, thus HPV infection and HPV+ cancer still requires effective therapeutic interventions. There is currently no available therapy treating HPV specifically.
Vaccibody is a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel immunotherapies. The company is one of the leaders in the rapidly developing field of individualized cancer neoantigen vaccines and is using the Vaccibody technology to generate best-in-class therapeutics to treat cancers with a high unmet medical need. A phase I/IIa neoantigen clinical trial is currently enrolling patients with locally advanced or metastatic melanoma, non-small cell lung carcinoma, clear renal cell carcinoma as well as urothelial or squamous cell carcinoma of the head and neck. Vaccibody’s most advanced program (VB10.16) is a therapeutic DNA vaccine against HPV16 induced pre-malignancies and malignancies. Further information about the company and its drug development programs and capabilities may be found online at http://www.vaccibody.com
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