E!10480 A FAS ligand hexameric (APO010) and companion diagnostics in the immunotherapy of multiple myeloma.

BACKGROUND AND PLAN Smerud Medical Research International AS, which is a European drug development company with headquarters in Norway, and Danish biotech company Oncology Venture ApS have joined forces to develop a new drug (APO010) intended to treat multiple myeloma. Multiple Myeloma (bone marrow cancer) is a systemic malignancy in the blood, affecting plasma cells. In spite of introduction of new therapies in recent years, eventually all patients will experience progressive disease and continue into second and later lines of treatment. APO010 has a unique mechanism of action, and was well tolerated when tested in 25 patients with solid tumors. As pre-clinical studies have revealed that APO010 is highly efficient in Multiple Myeloma, we will conduct a clinical proof of concept trial in patients with Multiple Myeloma that have been pre-screened for sensitivity using the APO010 DRP technology. The DRP (Drug Response Predictor) platform is a companion diagnostic using genomic information from the individual cancer patient's tumor. About 150 patients will be screened, and those 15 patients with the highest likelihood to benefit from treatment with APO010 will then be included in a prospective multi-center clinical phase 2 trial exploring early signals of efficacy. The study will be conducted in University Hospitals in Northern Europe. The study is approved and is running in Denmark. Teh project will continue outside the Eurostars project. Other indications can be explored.

The DRP screening of multiple myeloma patients has been advanced during this project. There has been further method development and we have obtained clinical data important for validation of the method. The DRP method has also be developed in combination with other drugs used in treatment of multiple myeloma patients that can be used for a better selection of treatment for individual patients. Unfortunately the phase I proof-of-concept study has not been possible to complete during the project period. The clinical proof-of concept study is still on-going and the outcome of this is still not known.

We aim to advance a new immunotherapy drug (APO010) to clinical proof of concept in the treatment of multiple myeloma (MM) by using an advanced Drug Response Predictor (DRP) analysis, based on genomic information combined with clinical tumor biology and clinical correlates in a systems biology network, as a Companion Diagnostic (CDx). APO010-sensitive patients will undergo a prospective clinical trial of APO010 exploring early efficacy signals and tolerability in a highly selected patient group. Despite introduction of new treatments in later years, multiple myeloma patients will eventually experience progressive disease, so there is a huge medical need for new drugs. The executioner in immuno-oncology is the cytotoxic T-Cell, but immunotherapy remains a challenge in tumors with few infiltrating lymphocytes as in MM. Thus, APO010 is being developed, as it uses the cytotoxic T Cell tumor killing mechanism as an immunotherapy executioner. Introducing immunotherapy in MM through clinical proof-of-concept (cPoC) will add significant value to the product, and take out a lot of the risk prior to later pivotal, confirmatory clinical trials. Reaching cPoC in the Eurostars project will enable us to commercialize the venture by raising private equity and fund a special vehicle biotech company to take APO010 through the first phase 2 trial, before licensing out development and/or marketing rights to a bigger, global pharma partner.