Broad pipeline with four assets planned to be in clinical development by the end of 2019

 
 

Clinical and Pre-Clinical Pipeline Overview 

GEMoaB has a broad pipeline of product candidates in preclinical and clinical development for the treatment of hematological malignancies as well as solid tumors. Our lead clinical stage assets GEM333, an affinity-tailored adaptor for T-Cells (ATAC) with binding specificity to CD33 against relapsed/refractory acute myeloid leukemia, and GEM3PSCA, an ATAC with binding specificity to PSCA for the treatment of refractory castrate-resistant metastatic prostate cancer as well as pancreatic, breast, bladder, renal and non-small cell lung cancer, are currently in Phase I studies. GEM333 and GEM3PSCA are globally partnered with Celgene.

 
 
Asset Indication Target Pre-Clinical Phase I Planned IND Planned FPI
GEM333* rrAML CD33
GEM3PSCA* met. NSCLC, CRPC, bladder Ca, renal Ca, pancreatic Ca, breast Ca PSCA
UniCAR-T-CD123 rrAML, rrALL, rrBPDCN CD123 H2/2019
UniCAR-T-PSMA met. CRPC, other PSMA-expressing solid tumors PSMA H2/2019 H2/2019
UniCAR-T 3 Neurondocrine Tumors undisclosed H2/2020
RevCAR 1 Colorectal Ca, CRPC, pancreatic Ca, stomach Ca, NSCLC, breast Ca undisclosed H2/2020
RevCAR 2 (allogeneic)* undisclosed undisclosed H1/2021
UniCAR-T 4 AML, multiple myeloma undisclosed H1/2021
ATAC 3* undisclosed undisclosed H2/2021

*partnered

 

Clinical Development Plans

GEM333 Development Highlights

Therapeutic approach

  • CD33 is a myeloid differentiation antigen, broadly expressed on AML blasts and possibly some leukemic stem cells, but not on normal hematopoietic stem cells

  • A CD33-ADC (gemtuzumab ozogamicin; Mylotarg®) is approved in AML

  • About 85-90% of AML patients show CD33 antigen expression

GEM333 pharmacology

  • Humanized scBsTaFv (CD33-CD3) binds CD33 on myeloid cells and AML blasts and CD3ε on TCR complex

  • Specific lysis of CD33+ cells observed at very low concentrations in in-vitro and in-vivo experiments

  • The CD3 binder does not auto-activate T-Cells in the absence of target cells

GEM333 safety profile/toxicology

  • The short half-life (1h) and continuous infusion delivery allow for immediate interruption of administration in the event of AEs

GEM333 commercial differentiation

  • Fully humanized, unique CD3 binder that shows no auto-activation of T-Cells

  • No prophylactic use of Dexamethasone

  • Potential differentiation to conventional T-Cell engagers which showed severe CRS events even at very low doses

Additional key facts

  • Potential for best-in-class safety

  • Potential for multiple future combination strategies (e.g. with targeted therapies such as FLT-3 inhibitors), usage in 1st line AML as well as high-risk MDS

  • 25,000 rrAML patients in US and Europe, lack of Standard of Care (SoC) representing a significant commercial opportunity

  • Regulatory opportunity for Orphan Drug Designation (ODD) and accelerated approval pathways in US and Europe under evaluation

  • Globally partnered with Celgene Corporation

For further details visit ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT03516760

 

GEM3PSCA Development Highlights

Therapeutic approach

  • Prostate stem cell antigen (PSCA) is broadly expressed across solid tumors including pancreatic, breast, renal cell, urothelial, prostate and non-small cell lung carcinoma (25-95%)

  • In normal tissues, PSCA expression is mostly restricted to the apical side of epithelia (most critical: bronchus, urether and bladder)

GEM3PSCA pharmacology

  • Humanized scBsTaFv (CD3-PSCA) binds PSCA on PSCA+ tumor cells and CD3ε on TCR complex

  • Specific lysis of PSCA+ cells is observed at very low concentrations in in-vitro and in-vivo experiments

  • The CD3 binder does not auto-activate T-Cells in the absence of target cells

GEM3PSCA safety profile/toxicology

  • The short half-life (1h) and continuous infusion allow for immediate interruption of administration in the event of AEs

GEM3PSCA commercial differentiation

  • Fully humanized, no auto-activation of T-Cells and short half-life – bears the potential for a best-in-class safety profile

Additional key facts

  • Covering a broad cancer spectrum of hard-to-treat late-stage tumors with limited SoC, thus representing a significant commercial opportunity

  • Potential for multiple future combination strategies

  • First patient treated in July 2019

  • Regulatory opportunity for ODD and accelerated approval pathways in US and Europe under evaluation

  • Globally partnered with Celgene

For further details visit ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT03927573

 

UniCAR-T-CD-123 DEVELOPMENT HIGHLIGHTS

Therapeutic approach

  • CD123 (alpha chain of IL-3 receptor) is broadly expressed on myeloid and lymphoid stem and progenitor cells and therefore a logical and validated target for rrAML, rrALL and rrBPDCN

UniCAR-T-CD123 pharmacology

  • The UniCAR platform is a next-generation modular CAR technology with “switch on/switch off” mechanism allowing a repeated stop-go CAR-T therapy to increase patient safety

  • Autologous human T-Cells are genetically modified to UniCAR-T and re-infused into patients

  • A recombinant protein adaptor (Targeting Module) termed TM123 is co-administered to patients. UniCAR-T-Cells are cross-linked to CD123-expressing leukemic cells by TM123 and eliminate targeted cells

UniCAR-T-CD123 safety profile/toxicology

  • Primary objective of the phase I dose-finding trial will be to assess the safety and to determine the MTD dose and the incidence of dose-limiting toxicities (DLT) during the DLT period

  • Secondary objectives are to determine the RP2D efficacy in terms of reduction in bone marrow blasts, best response rate, CR/PR rate, remission duration, progression free survival and overall survival

  • Main expected side effects will be neutropenia and lymphocytopenia, due to the switch-off mechanism a low incidence of CRS and CNS events is to be expected

UniCAR-T-CD123 commercial differentiation

  • Due to the switch on/switch off mechanism, UniCAR-T-123 bears the potential of a best-in-class safety profile

  • With 25,000 rrAML and 10,000 rrALL patients in US and Europe – more than 75% being CD123-positive – and a lack of SoC post standard therapies represent significant commercial opportunity

Additional key facts


  • Regulatory opportunity for ODD and accelerated approval pathways in US and Europe under evaluation

A Phase I dose finding study of UniCAR-T-CD123 in CD123 positive rrAML, rrALL and rrBPDCN is planned to start recruitment by H2/2019.

 

UniCAR-T-PSMA DEVELOPMENT HIGHLIGHTS

Therapeutic approach

  • PSMA is expressed on normal and malignant prostate cells; expression levels are higher on malignant cancer cells and increase with disease progression

  • 70% of metastatic CRPC patients express high levels of PSMA

  • PSMA is also expressed in the neovasculature of multiple solid tumors including NSCLC

UniCAR-T-PSMA pharmacology

  • The UniCAR platform is a next-generation modular CAR technology with “switch on/switch off” mechanism allowing a repeated stop-go CAR T therapy to increase patient safety

  • Autologous human T-Cells are genetically modified to UniCAR-T and reinfused into patients

  • A peptide adaptor (Targeting Module) termed TMpSMA is co-administered to patients. UniCAR-T cells are cross-linked to PSMA-expressing tumor cells by TMpPSMA and eliminate targeted cells

UniCAR-T-PSMA safety profile/toxicology

  • Primary objective of the phase I dose-finding trial will be to assess the safety and to determine the MTD dose and the incidence of dose limiting toxicities (DLT) during the DLT period

  • Secondary objectives are to determine the RP2D efficacy in terms of response rate, CR/PR rate, remission duration, progression free survival and overall survival

  • Due to the switch-off mechanism a low incidence of CRS and CNS events is to be expected

UniCAR-T-PSMA commercial differentiation

  • Due to the switch on/switch off mechanism, UniCAR-T-PSMA bears the potential of a best-in-class safety profile

  • With 60,000 CRPC patients post chemotherapy and AR-antagonists alone – 80% being PSMA positive – and a lack of SoC post standard therapies representing significant commercial opportunity

Additional key facts

  • Regulatory opportunity for ODD and accelerated approval pathways in US and Europe under evaluation

A Phase I dose finding study of UniCAR PSMA in met. CRPC and other PSMA expressing solid tumors is planned to start recruitment by H2/2019.

 
 

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Publications on our ATAC and UniCAR/UniREV Platforms
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