iRASP - A unique platform for the discovery of new tumor-specific therapeutic antibodies

Challenge

Antibody-based immunotherapies have dramatically changed the natural history of several cancer types. However, due to the difficulty to predict in vivo accessibility of the tumor-associated antigens discovered by the standard target-first approach, only a small number of antibody-based drugs have entered into clinical use. Furthermore, more than 50% of the available therapeutic antibodies target only a few antigens, with the result that the majority of cancer types have no targeted immunotherapeutic option. Therefore, it is pivotally important to design immunotherapies against novel tumor-associated antigens, to achieve efficacious therapy for currently untreatable tumors.

Technology

We have developed an innovative in vivo Recombinant Antibody-Screening Platform (iRASP) based on the antibody-first strategy that allows to unbiasedly identify tumor-specific therapeutic antibodies, without prior knowledge of their target antigens. iRASP innovatively integrates a novel in vivo phage display method to exclusively isolate in vivo tumor-binding phage antibodies, with a reliable and robust selection process allowing to prioritize the selected in vivo tumor-binders on the basis of their relative frequency and specificity for tumor cells. Such high-throughput, rapid workflow can be tailored and applied to virtually any tumor type for the development of new tumor-targeted antibody therapies, and it also allows to simultaneously identify both the new antibody candidates and their cancer-associated targets.

Commercial Opportunity

We are now seeking partners interested in further exploiting the iRASP platform through the creation of a dedicated start-up focused on discovery of new therapeutic antibodies for oncological indications with high unmet medical need. The start-up will sustain the product development process from discovery to the in vivo proof of concept. Lead candidates will be out-licensed for their further development towards the clinic. The iRASP platform has the high potential to provide new antibody-based immunotherapies for cancer patients, thus placing the future start-up in the growing global cancer immunotherapy market.

Development Status

iRASP technology platform has been validated through the identification of three therapeutic candidates for refractory T-cell acute lymphoblastic leukaemia (T-ALL). In vivo proof of concept data demonstrate that the three antibodies are therapeutically effective both as bare antibodies and antibody-cytokine fusions. New candidates have been isolated in other 5 oncological indications with high unmet medical need. The inventors are now engaged in (i) further characterization and preclinical development of the three validated T-ALL antibodies and (ii) in vivo proof of concept studies of two recently isolated candidates against acute myeloid leukemia (AML).

Patent Situation

PCT/EP2019/066217 (method and product), pending in US and EP Filing of new composition of matter patents (newly discovered candidates.

Further Reading

• Byrne AT, Alférez DG, Amant F, et al. Interrogating open issues in cancer precision medicine with patient-derived xenografts. Nat Rev Cancer. 2017;17(4):254–268. doi:10.1038/nrc.2016.140
• WO2019243428 (A1). ISTITUTO EUROPEO DI ONCOLOGIA SRL [IT]. Antibodies anti-tumor associated antigens and method for obtaining them.