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1333 Development of IMGS-001, a novel anti-PD-L1/PD-L2 dual specific, multi-functional antibody, to treat immune excluded tumors
  1. Christine Gagliardi1,
  2. Federica Pericle1,
  3. Ahmad Salameh1,
  4. Paul Blezinger1 and
  5. Michael Curran2
  1. 1ImmunoGenesis, Inc., Houston, TX, USA
  2. 2MD Anderson Cancer Center, Houston, TX, USA


Background Interruption of the programmed cell death-1 (PD-1) inhibitory pathway by binding PD-1 or its ligand PD-L1 is an effective treatment for various cancers,1 although resistance is common.2 PD-1 has a second ligand, PD-L2, that can be expressed by a variety of immunosuppressive stromal cells, endothelial cells, and tumor cells.3 IMGS-001 is a dual specific monoclonal antibody designed to bind PD-L1 and PD-L2 and block their engagement with PD-1. The Fc region is engineered to induce robust cell-mediated cytotoxicity, enabling depletion of PD-L1+ and PD-L2+ immunosuppressive cells throughout the tumor microenvironment. Here we describe the development of IMGS-001, including potency, specificity, cytokine release potential, pharmacokinetics (PK), and repeat-dose toxicity

Methods Affinities were measured with the Octet system. Reporter cell assays assessed PD-1 pathway blockade, antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). Specificity was evaluated by Retrogenix microarray technology. Potential for spontaneous cytokine release was measured by co-culturing with healthy donor peripheral blood mononuclear cells. PK was measured in mice and in cynomolgus monkeys. In a GLP toxicity study, IMGS-001 was dosed weekly over 4 weeks at 10, 50, or 100mg/kg with a 4-week recovery.

Results The affinity of IMGS-001 to monomeric PD-L1 and PD-L2 is 7.62nM and 1.90nM, respectively. Dimer affinities are 1.28nM and 600pM. It has an EC50 of 0.3-1.1nM in a PD-1 blockade assay, the same range as pembrolizumab and avelumab. IMGS-001 has an EC50 of <0.5nM in ADCC and ADCP assays. Specificity screening showed no relevant off-target binding and there was no evidence of specific cytokine release. Mouse PK showed drug exposure of ~1.0x104 µg-hr/ml at the efficacious dose. Half-life was 3.2 days in mice, and 3.7 days in cynos. Repeat-dose toxicity showed mild to moderate hematological and pathological changes, all of which had evidence of reversal within the recovery period. IMGS-001 was manufactured with a titer of 5.95g/L, 98.9% monomer, and 98% purity in the first GMP batch.

Conclusions These data indicate that IMGS-001 binds PD-L1 and PD-L2 and functions per its design. It shows no biologically relevant off target effects, was administered up 100 mg/kg without toxicity, and has a viable PK profile for human administration. It’s mechanisms of elimination of immunosuppressive cells with PD-1 pathway blockade could benefit patients that are resistant to existing PD-(L)1 drugs by restoring immune driven anti-tumor activity. IMGS-001 is poised to enter clinical trial in immune excluded tumors by the end of 2022.


  1. Alsaab HO, Sau S, Alzhrani R, Tatiparti K, Bhise K, Kashaw SK, & Iyer AK. PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome. Front Pharmacol. 2017;8:561.

  2. Syn NL, Teng M, Mok T, & Soo RA. (2017). De-novo and acquired resistance to immune checkpoint targeting. Lancet. Oncol. 2017;18(12):e731–e741.

  3. Yearley JH, Gibson C, Yu N, Moon C, Murphy E, Juco J, Lunceford J, Cheng J, Chow L, Seiwert TY, Handa M, Tomassini JE, & McClanahan T. (2017). PD-L2 Expression in Human Tumors: Relevance to Anti-PD-1 Therapy in Cancer. Clin Cancer Res. 2017;23(12):3158–3167.

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