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

Smerud Medical Research International AS er et norskeiet selskap som utvikler legemidler, og sammen med det danske biotek-firmaet Oncology Venture ApS vil man i dette prosjektet utvikle legemiddelkandidaten APO010 som immunterapi ved myelomatose. Myelomatose er en type kreft i en bestemt gruppe av benmargens celler, nemlig plasmacellene. Til tross for at nye behandlinger har blitt introdusert de senere år, vil alle pasienter etterhvert få progressiv sykdom og ny behandling vil bli påkrevet. APO010 har en unik virkningsmekanisme, og ble godt tolerert i en studie med 25 pasienter med solide tumorer. Dyreforsøk har vist at APO010 er svært effektiv mot myelomatose og vi planlegger derfor nå en klinisk fase 2 studie med slike pasienter. Basert på ny teknologi som analyserer genetisk informasjon i tumorvevsprøver fra den enkelte pasient, en såkalt Drug Response Predictor, kan man nå på forhånd anslå om den enkelte pasient vil reagere positivt på behandling med APO010 eller ikke. Omtrent 150 pasienter med myelomatose vil bli screenet, og de 15 av disse som antas å ha best effekt av APO010, vil gjennomgå en prospektiv klinisk utprøvning med APO010 for å se etter tidlige bevis på effekt. Studien vil utføres på utvalgte universitetssykehus i Nord-Europa. Studien er godkjent og pågår i Danmark. Prosjektet vil fortsette etter Eurostars prosjektet er avsluttet. Andre indikasjoner kan blir vurdert.

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.