Publication underscores ImCheck’s pioneering role in Vγ9Vδ2 T cell-based immunotherapy capable of bridging to the adaptive antitumor immune response through a novel family of immune checkpoint targets
Evaluation details ICT01’s progression from bench to bedside describing factors that enabled ICT01 to overcome limitations of prior efforts to activate Vγ9Vδ2 T cells for the treatment of cancer
Marseille, France, October 20, 2021 – ImCheck Therapeutics announced today the publication of the preclinical to clinical development of its lead immuno-oncology program, ICT01. The publication in the medical journal Science Translational Medicine details ImCheck’s butyrophilin (BTN)-based immuno-oncology approach and positions ImCheck as a pioneer in a nascent field of immunomodulation. ICT01 is a fully-humanized anti-BTN3A monoclonal antibody designed to selectively activate gamma 9 delta 2 (Vγ9Vδ2) T cells through all three isoforms of BTN3A (1/2/3), which are expressed on the surface of innate and adaptive immune cells and overexpressed on the tumor cells of a number of solid and hematologic cancers.
The article, titled “Development of ICT01, a first-in-class, anti-BTN3A antibody for activating Vγ9Vδ2 T cell-mediated anti-tumor immune response” describes the molecular mechanism of how ICT01 activates Vγ9Vδ2 T cells in a pAg-independent and BTN3A isoform-agnostic manner, overcoming the two key limitations of prior efforts to activate Vγ9Vδ2 T cells. In the first-in-human EVICTION Phase I/IIa clinical trial, ICT01 demonstrated selective activation of Vγ9Vδ2 T cells, causing them to rapidly migrate out of the circulation and into tumor tissue. Furthermore, ICT01-activated Vγ9Vδ2 T cells secrete IFNγ and TNFa that expands the anti-tumor immune response by recruiting CD3 and CD8 T cells into tumors.
“This very comprehensive publication describes the bench-to-bedside story of ICT01 and presents in detail ImCheck’s novel and differentiated immunotherapeutic approach,” said Paul Frohna, PharmD, Chief Medical Officer of ImCheck. “ICT01’s unique design circumvents prior limitations of activating Vγ9Vδ2 T cells in cancer patients, making it a promising candidate for the treatment of a broad range of cancers. We look forward to building upon these published results in an upcoming presentation at the SITC 2021 Annual Meeting.”
“Our mission is to apply our scientific expertise and clinical leadership with the BTN superfamily of immunomodulators to bring innovative therapeutics to patients. The publication of these findings in Science Translational Medicine exemplifies our leadership in BTN research as a promising avenue of investigation for cancer immunotherapy and supports the further development of our pipeline of other BTN-targeted programs,” stated Pierre d’Epenoux, Chief Executive Officer of ImCheck Therapeutics.
The publication was authored by ImCheck scientists in collaboration with the laboratory of Prof. Daniel Olive, Professor of Immunology and Director of the Oncology Research Programs at Aix Marseille University and the company’s scientific founder.
ICT01 is a humanized, anti-BTN3A (also known as CD277) monoclonal antibody that selectively activates Vγ9Vδ2 T cells, which are part of the innate immune system that is responsible for immunosurveillance of malignancy and infections. The three isoforms of BTN3A targeted by ICT01 are overexpressed on a number of solid tumors (e.g., bladder, colorectal, melanoma, ovarian, pancreatic, lung) and hematologic cancers (e.g., leukemia & lymphoma) and also expressed on the surface of innate (e.g., γδ T cells and NK cells) and adaptive immune cells (T cells and B cells). BTN3A is essential for the activation of the anti-tumor immune response of Vγ9Vδ2 T cells.
As demonstrated in EVICTION data presented at AACR, ICT01 selectively activates circulating Vγ9Vδ2 T cells that leads to migration of Vγ9Vδ2 T cells out of the circulation and into target tissue (e.g., tumors), while also activating the tumor-resident Vγ9Vδ2 T cells to directly kill malignant cells, which is accompanied by secretion of two key inflammatory cytokines, IFNg and TNFa, that contribute to the expansion of the anti-tumor immune response. ICT01 has been shown to have anti-tumor activity against a range of cancers in in vitro and in vivo tumor models.
About the EVICTION Trial
EVICTION is a first-in-human, dose escalation (Part 1) and cohort expansion (Part 2) clinical trial of ICT01 in patients with various advanced relapsed or refractory solid or hematologic cancers that have exhausted standard of care treatment options. Part 1 is a basket trial designed to characterize the preliminary safety, tolerability, and pharmacodynamic activity of ICT01 as monotherapy (Group A: solid tumors; Group B: hematologic tumors) and in combination with pembrolizumab (Group C: solid tumors). Group A includes bladder, breast, colorectal, gastric, melanoma, ovarian, prostate, and pancreatic cancer patients, Group B includes acute myeloid leukemia, acute lymphocytic leukemia, follicular lymphoma, and diffuse large B cell lymphoma patients, and Group C includes bladder, head and neck squamous cell carcinoma, melanoma, and non-small cell lung cancer patients. Basket trials are a clinical trial design that allows new drugs to be tested rapidly in a range of indications, providing initial data on multiple parameters that can contribute to an accelerated development timeline. More information on the EVICTION trial can be found at clinicaltrials.gov (NCT04243499).
About IMCHECK THERAPEUTICS
ImCheck Therapeutics is designing and developing a new generation of immunotherapeutic antibodies positioned at the crossroads of two high-potential immunological fields: γ9δ2 T cells and butyrophilins (BTN), a novel super-family of checkpoint molecules.
Due to their mechanism of action, and notably their ability to simultaneously modulate innate and adaptive immunity, ImCheck's “first-in-class” activating antibodies may be able to produce superior clinical results as compared to the first-generation of immune checkpoint inhibitors and when used in combination to overcome the resistance to this group of agents. In addition, preclinical experiments with ImCheck’s antagonist antibodies are being evaluated as potential treatments for autoimmune diseases.
Co-founder of the Marseille Immunopole cluster, ImCheck benefits from support from Prof. Daniel Olive (INSERM, CNRS, Institut Paoli Calmettes, Aix-Marseille Université), a worldwide leader in γδ T cells and butyrophilins research; from the experience of an expert management team; and from the commitment of leading US and European investors.
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Science Translational Medicine
Method of Research
Randomized controlled/clinical trial
Subject of Research
Development of ICT01, a first-in-class, anti-BTN3A antibody for activating Vγ9Vδ2 T cell-mediated anti-tumor immune response
Article Publication Date
ADG, KSL, PB, SA, EV, CG, MC, JG, CEC and PF are employees and shareholders of ImCheck Therapeutics. CP and RH are a former employee of ImCheck Therapeutics. JS received consulting fees from ImCheck Therapeutics. DO is a co-founder of ImCheck Therapeutics, Alderaan Biotechnology and Emergence Therapeutics and has research funds from ImCheck Therapeutics, Alderaan Biotechnology, Cellectis and Emergence Therapeutics. AT is a co-founder and advisor of ImCheck Therapeutics. DO and ES are co-inventor on the patent application PCT/WO2012080769A1 for “Anti-cd277 antibodies and uses thereof”. ADG, AT, CP and DO are co-inventors on the patent application PCT/WO2020025703A1 for “Anti BTN3A antibodies and their use in treating cancer or infectious Disorders”.