BTN3A1

ImCheck Receives FDA Fast Track Designation for ICT01in Combination with Azacitidine and Venetoclaxin First-Line Acute Myeloid Leukemiafor Patients Unfit for Induction Chemotherapy Treatment ICT01, a humanized anti-butyrophilin 3A monoclonal antibodydesigned to selectively activate Vγ9Vδ2 T cells, has shown encouraging clinical datain AML in its ongoing Phase 1/2a EVICTION study Marseille, France, September 18, 2024, 11 am CET – ImCheck Therapeutics announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ICT01 in combination with azacitidine and venetoclax for the treatment of acute myeloid leukemia (AML) patients 75 years or older, or who have comorbidities that preclude use of standard intensive induction chemotherapy. Based on encouraging results from the Phase 1 dose-escalation portion of the EVICTION study evaluating ICT01 monotherapy in relapsed/refractory hematological malignancies (European Society for Medical Oncology Congress 2023), ImCheck initiated in October 2023 a randomized dose-optimization cohort (NCT04243499), evaluating two doses of ICT01 in combination with azacitidine and venetoclax, the current standard of care for newly diagnosed patients with AML who are deemed unfit for induction chemotherapy. “The growing body of data on ICT01 together with the FDA’s Fast Track designation further validates our development of ICT01 in first-line AML patients and highlights the critical need for therapies that generate higher response rates and improve overall survival for these patients,” said Stephan Braun, MD, PhD, Chief Medical Officer of ImCheck Therapeutics. “We are highly encouraged by ICT01’s potentially broad applicability in solid tumor and hematological cancer indications and look forward to sharing updates from the EVICTION study at upcoming scientific conferences.” The FDA designed Fast Track status to facilitate the development and expedite the review of therapeutic candidates that have the potential to treat serious conditions and address an unmet medical need. A therapeutic candidate that receives Fast Track designation may be eligible for more frequent interactions with the FDA to discuss the candidate’s development plan. Candidates with Fast Track designation may also be eligible for Priority Review and Accelerated Approval if supported by clinical data, with the goal of bringing approved therapies to patients earlier. EVICTION is an open-label multicohort Phase 1/2a trial studying ICT01, a humanized anti-butyrophilin 3A monoclonal antibody that selectively activates γ9δ2 T cells; the study comprises cohorts investigating ICT01 as a monotherapy and combination therapy in solid and hematological tumors. As reported at ESMO 2023, the Phase 1 dose-escalation cohort in relapsed/refractory hematological cancers included 26 patients who failed all available treatment options, 24 of which had AML, one with diffuse large B-cell lymphoma and one with follicular lymphoma. No dose-limiting toxicities were revealed for ICT01 administered at doses ranging from 200 μg to 75 mg every 21 days. Based on encouraging safety, pharmacokinetic and pharmacodynamic data, a dose-optimizing and efficacy-estimating part was initiated for patients with newly diagnosed AML who are older or deemed unfit for standard chemotherapy, which has enrolled 29 patients to date. Emerging pharmacodynamic and pharmacokinetic data for ICT01 in combination with azacitidine-venetoclax showed reproducible activation and migration of γ9δ2 T cells from the blood within hours of dosing, suggesting effective target engagement as the basis for the observed efficacy. *** About IMCHECK THERAPEUTICS ImCheck Therapeutics is designing and developing a new generation of immunotherapeutic antibodies targeting butyrophilins, a novel super-family of immunomodulators. As demonstrated by its lead clinical-stage program ICT01, which has a mechanism of action 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 resistance to this group of agents. In addition, ImCheck’s antagonist antibodies are being evaluated as potential treatments for a range of autoimmune and infectious diseases. ImCheck benefits from support from Prof. Daniel Olive (INSERM, CNRS, Institut Paoli Calmettes, Aix-Marseille University), a worldwide leader in γ9δ2 T cells and butyrophilins research, as well as from the experience of an expert management team and from the commitment of leading US and European investors. For further information: https://www.imchecktherapeutics.com/ Press contacts: US and EU Trophic CommunicationsGretchen Schweitzer +49 (0) 172 861 8540imcheck@trophic.eu FranceATCG PARTNERSCéline Voisin+33 (0)9 81 87 46 72 / +33 (0)6 62 12 53 39imcheck@atcg-partners.com Attachment PR in English

The latest funding is the fifth consecutive time ImCheck has received financial support from the French government. Image Credit: Mer_Studio / Shutterstock. ImCheck Therapeutics has received €20.18m ($22.35m) in non-dilutive funding from the French government to advance its pipeline. The funds were disbursed as part of the “i-Démo” call for projects under the France 2030 Plan operated by Bpifrance on behalf of the French government. The public capital will be used to advance ImCheck’s clinical pipeline consisting of a T cell-activating monoclonal antibody and an infectious disease therapy. The French company’s lead candidate is ICT01, a pathogen-agnostic γ9δ2 T cell-activating monoclonal antibody targeting BTN2A, also known as CD277. It is being evaluated in multiple solid tumours and blood cancer indications in Phase I/IIa trials . The company is also investigating ICT01 in combination with Merck &Co (MSD)’s checkpoint inhibitor Keytruda (pembrolizumab) in patients with refractory solid tumours. The interim data from 21 patients with refractory melanoma enrolled in the Phase I/II EVICTION study (NCT04243499) showed three atrial responses at 16 weeks. A disease control rate of 21% was also observed with the combination therapy. The most common adverse events were grade 1-2 in intensity and included infusion-related reactions and cytokine release syndrome. Another open-label study, the Phase I/II EVICTION-2 trial (NCT05307874), is evaluating ICT01 and Clinigen ’s low-dose subcutaneous interleukin-2 therapy, Proleukin (aldesleukin), in patients with advanced solid tumours. In November 2023, ImCheck reported data showing that 19 patients have completed at least one cycle, with mild to moderate adverse events and no dose-limiting toxicities. See Also: Emergent gains FDA approval for ACAM2000 vaccine for Mpox EC approves GSK’s RSV vaccine for adults aged 50-59 years The latest funding influx is the fifth consecutive time ImCheck has received financial support from the French Government, whose plans have earmarked €54bn (59.8bn) for supporting strategic sectors. This includes healthcare as part of the France 2030 Investment Plan . ImCheck also plans to funnel resources to advance an anti-BTN2A agnostic γ9δ2 T cell-activating monoclonal antibody, ICT41, as a therapy for bacterial and viral infections. The recent mpox outbreak has seen a rise in investment in infectious diseases. Earlier this week, the US Food and Drug Administration expanded the label for Emergent BioSolutions ’ mpox vaccine, ACAM2000.

ImCheck to Present Promising ICT01 Datafrom the EVICTION Study at ASCO 2024 Interim data from Phase I/II EVICTION study shows favorable safety profile and promising efficacy for ICT01 in combination with pembrolizumab in refractory melanoma patients Marseille, France, May 30, 2024, 11 am CET – ImCheck Therapeutics announced today that updated data from its ongoing Phase I/II study EVICTION will be presented in a poster session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting being held in Chicago. The poster will provide new data from the study assessing ICT01, a humanized anti-BTN3A monoclonal antibody that selectively activates γ9δ2 T cells, in combination with checkpoint inhibitor (CPI) pembrolizumab. The results, specifically in patients with CPI-refractory melanoma, support the therapeutic potential of the ICT01‒pembrolizumab combination. “Our objective with the EVICTION study is to validate ICT01’s promise as an innovative therapy and inform the next steps of its clinical development. The data presented at ASCO further define ICT01’s therapeutic potential, in particular in combination with pembrolizumab, where we see promising data in CPI-refractory patients. ImCheck intends to further investigate this combination regimen in refractory solid tumors, where patients have limited treatment options,” commented Pierre d’Epenoux, Chief Executive Officer of ImCheck Therapeutics. Data from EVICTION presented at ASCO will include full safety data from all cohorts and preliminary efficacy data from ongoing assessments performed every 8 weeks in patients with metastatic melanoma. ICT01‒pembrolizumab combination treatment showed a clinically manageable safety profile with generally mild and clinically manageable first-dose Grade 1/2 infusion-related reactions (38%) and cytokine release syndrome (19%) as the most common adverse events across all doses and indications. In the CPI-refractory melanoma group, 21 patients were evaluable at week 16 with 3 partial responses and a disease control rate of 42%. In addition, biomarker analyses revealed clinical response was associated with baseline BTN3A tumoral expression, sustained elevation of IFNɣ levels, and tumor microenvironment remodeling. Based on these findings, biomarker-driven patient selection will be further investigated as a potential enrichment strategy. Details of the poster presentation are:Abstract title: “EVICTION study: ICT01, an anti-Butyrophilin 3A monoclonal antibody activating γ9δ2 T cells in combination with pembrolizumab in checkpoint inhibitor refractory melanoma.”Session title: Melanoma/Skin CancersAbstract number: 9534Poster board: 318Presenter: Dr Stephane Champiat, Gustave RoussyAuthors: Stephane Champiat, Martin Wermke, Cecile Vicier, Johann S. De Bono, Emiliano Calvo, Jorge Ramón, Evan Thomas Hall, Elena Garralda, Vladimir Galvao, Emanuela Romano, Antoine Italiano, Esma Saada, Benoit You, Aude De Gassart, Maelle Mairesse, Emmanuel Valentin, Patrick Brune, Daniel Olive, Katrien Lemmens, Paul FrohnaDate/Time: Saturday June 1st, 2024, 1:30–4:30 pm CSTLocation: Hall A - McCormick Place The ASCO poster will be available on ImCheck’s corporate website after the presentation has been completed. *** About the EVICTION StudyEVICTION is a first-in-human, dose escalation (Part 1) and cohort expansion (Part 2) clinical study 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. Part 2 of the trial is a Phase II cohort expansion study in selected indications as both monotherapy and in combination. First indications selected for the Phase II monotherapy expansion cohorts are relapsed/refractory ovarian cancer and metastatic castrate-resistant prostate cancer. More information on the EVICTION study can be found at clinicaltrials.gov (NCT04243499). A second clinical study, EVICTION-2, evaluating the combination of ICT01 plus low dose subcutaneous IL-2 to selectively expand the number of γ9δ2 T cells in patients with solid tumors (prostate, pancreatic, ovarian, or colorectal cancer) is also ongoing (NCT05307874). About ICT01ICT01 is a humanized, anti-BTN3A (also known as CD277) monoclonal antibody that selectively activates γ9δ2 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 γ9δ2 T cells. As demonstrated in EVICTION data presented at past AACR, EMSO and SITC conferences, ICT01 selectively activates circulating γ9δ2 T cells that leads to migration of γ9δ2 T cells out of the circulation and into target tissue (e.g., tumors), while also activating the tumor-resident γ9δ2 T cells to directly kill malignant cells, which is accompanied by secretion of two key inflammatory cytokines, IFNγ and TNFα, 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 IMCHECK THERAPEUTICS ImCheck Therapeutics is designing and developing a new generation of immunotherapeutic antibodies targeting butyrophilins, a novel super-family of immunomodulators. As demonstrated by its lead clinical-stage program ICT01, which has a mechanism of action 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 resistance to this group of agents. In addition, ImCheck’s antagonist antibodies are being evaluated as potential treatments for a range of autoimmune and infectious diseases. ImCheck benefits from support from Prof. Daniel Olive (INSERM, CNRS, Institut Paoli Calmettes, Aix-Marseille University), a worldwide leader in γ9δ2 T cells and butyrophilins research, as well as from the experience of an expert management team and from the commitment of leading US and European investors. For further information: https://www.imchecktherapeutics.com/ Press contacts: US and EU Trophic CommunicationsGretchen Schweitzer +49 (0) 172 861 8540imcheck@trophic.eu FranceATCG PARTNERSCéline Voisin+33 (0)9 81 87 46 72 / +33 (0)6 62 12 53 39imcheck@atcg-partners.com Attachment PR in English