A painstaking validation process has been carried out using our first vaccine, Vx-001, composed of two separate peptides: the native cryptic peptide ARG-Vx001 (TERT572) and its optimized variant TYR-Vx001 (TERT572Y). This process included in vivo experiments in mice, in vitro experiments on human lymphocytes, and a large exploratory phase I/II clinical trial. Vx-001 vaccination of humanized mice protects them against tumor growth in vivo (J Clin Invest. 2004 113:425-33). Furthermore, Vx-001 induces anti-tumor immune responses by human lymphocytes in vitro. Vx-001 has completed a phase I/II trial with 33 patients with NSCLC extended to 83 patients with different cancers (mainly breast, prostate and pancreatic cancers) (Oncology. 2006;70:306-14, Journal of Clinical Oncology, 2007 19, 2729-34, ASCO 2008 abstract 3030, AACR 2008 abstract 2541, Ann. Oncol., 2012, 23: 442-9, Cancer Immunol. Immunother., 2012, 61: 157-68). The major conclusions of this phase I/II trial are the following:

1. Vx-001 is safe and well tolerated: only Grade I/II vaccine-related toxicity was observed in vaccinated patients (local skin reaction).

2. Vx-001 is very strongly immunogenic. Immune response was observed in the majority of evaluable patients (70%) and appeared as early as after the second vaccination. Immune response was maintained with vaccination boosts for a long time (4 years).

3. Very promising results were obtained in the exploratory analysis of efficacy. One patient (breast cancer) experienced complete response, three patients (two NSCLC and one HCC) experienced partial responses and 33 patients demonstrated disease stabilization for more than 6 months. Importantly, clinical outcome correlated with the immune response.

4. Analysis of the 33 patients with metastatic NSCLC showed that survival was clearly related to the developed immune response. Immune responders had a much longer survival than non immune responders (24.8 vs 6.9 months).

Vx-001 entered a phase IIb trial in NSCLC in August 2012

Vx-001 entered a randomized phase IIb clinical trial in HLA-A*0201 positive patients with TERT expressing NSCLC (stage IV and distant recurrent stage I-III) who controlled disease after first line chemotherapy. The primary endpoint is to compare survival rate at 12 months. Two hundred twenty patients will be randomized in 46 sites in five European countries. The duration of the study is estimated to 30 months (18 months of recruitment and 12 months of follow-up). The first patient was enrolled in August 2012.