GEMoaB has developed three proprietary next generation immunotherapy platforms – ATAC, UniCAR and RevCAR – which promise significant advantages over existing immunotherapies.
While impressive clinical responses have been obtained with existing bispecific T-Cell engagers and CAR-T therapies, there are still a number of challenges to be overcome and next generation T-Cell-based immunotherapies are urgently needed.
Immunotherapy Status Quo versus the Advantages of GEMoaB Platforms
High rate and marked severity of treatment related toxicities (on target/on tumor and on target/off tumor)
Switch on/off capability avoiding overshooting on target/on-off tumor effects while allowing functional effector and memory CAR-T-Cells to remain in the patient
Limited efficacy and safety of T-Cell-based therapies in solid tumors
Switch on/off capability allowing for minimizing side effect risks due to expression of antigen on healthy tissue
Rapid resistance mechanisms through antigen escape, clonal evolution and immune suppression (e.g. expression of PD-L1)
Simple multi-antigen targeting optionality by using highly flexible targeting modules (TMs)
Complicated and costly centralized manufacturing infrastructure, slow turnaround time and long development timelines
Automated production of single CAR-T effector cell against multiple antigens leading to significantly reduced manufacturing costs and short needle-to-needle time; optionality for decentralized production
Key features of our proprietary next generation immunotherapy platforms
Our highly differentiated therapeutic platforms ATAC, UniCAR and RevCAR promise significant advantages over existing immunotherapies, based on the following key features.
High binding affinity for targeted tumor antigen and lower affinity for CD3 on effector T-Cells reduces risk of T-Cell auto-activation, cytokine release syndrome (CRS) and CNS side effects
Short serum half-life enables rapid clearance in case of overshooting on target/on-off tumor and improves the safety profile
Half-life extended versions are in pre-clinical development for suitable targets/indications
Fully humanized bispecific antibodies reducing risk of immunogenicity
Binding of genetically modified T-Cell to tumor antigen via highly flexible targeting modules (TMs)
Switch on/off mechanism allowing for repeated stop-go CAR-T therapy to increase patient safety and prevent T-Cell exhaustion; combined or sequential use of TMs to counteract antigen escape mechanisms
Automated production of CAR T-Cell by our sister company Cellex allowing for significant reduction of turnaround time, infrastructure requirements and costs
GEMoaB – THREE HIGHLY DIFFERENTIATED THERAPEUTIC PLATFORMS
Our ATAC Platform
GEMoaB’s platform of Affinity-Tailored Adaptors for T-Cells (ATAC) is characterized by high binding affinity to tumor antigens and lower affinity to the CD3 antigen on effector T-Cells, preventing T-Cell auto-activation in pre-clinical models. Safety and tolerability of the treatment are also increased by the relatively short serum half-life (60 min). The use of fully humanized antibodies reduces the risk of immunogenicity even in case of chronic dosing. The first two clinical stage ATAC assets are GEM333 and GEM3PSCA.
GEM333 is an ATAC with binding specificities to CD3 and CD33, currently in early clinical development in CD33-positive relapsed/refractory acute myeloid leukemia (for further information see https://clinicaltrials.gov/ct2/show/NCT03516760). GEM3PSCA is an ATAC with binding specificities to CD3 and PSCA, currently in early clinical development in multiple PSCA-positive advanced solid tumors (see https://clinicaltrials.gov/ct2/show/NCT03927573). GEM333 and GEM3PSCA are globally partnered with Celgene. Half-life extended ATACs are in pre-clinical development.
Our UniCAR/RevCAR Platforms
To overcome toxicities as well as efficacy and manufacturing limitations of current CAR-T therapies, GEMoaB has established universal and modular chimeric antigen receptor (CAR) technologies called UniCAR and RevCAR. These genetically modified T-Cells can repeatedly be turned on and off via dosing of a Targeting Module (TM). TMs are mono-, bi- or multispecific molecules against diverse antigens, which crosslink UniCAR/RevCAR T-Cells with malignant target cells. After elimination of the respective TM, UniCAR/RevCAR T-Cells automatically and rapidly turn off. UniCAR uses an scFv-based binder attached to the CAR on the genetically modified T-cell, which recognizes the corresponding non-immunogenic peptide of the Targeting Module.
For the RevCAR platform, the CAR expressed on the genetically modified T-cell surface harbors a non-immunogenic peptide. RevCAR T-Cells are retargeted by bi-specific TMs, which harbor a scFv-based binder towards the peptide of the CAR and a binder directed against a tumor cell antigen. Our first two UniCAR assets, UniCAR-T-CD123 for treatment of relapsed/refractory AML and UniCAR-T-PSMA against CRPC and other PSMA-expressing late-stage solid tumors, are planned to be tested in Phase I studies initiated by H2 2019.
As patents are critical to GEMoaB’s business, we have filed a wide range of patent applications in Europe, the U.S., Japan, China, Canada and Australia to protect our innovative technologies and products. The patent family is continuously extended.