Immune-Onc Therapeutics Announces FDA Clearance of IND Application to Initiate First-In-Human Trial of IO-108, a Novel Antagonist Antibody Targeting LILRB2 (ILT4), in Patients with Advanced Solid Tumors

– Multicenter Phase 1 study to evaluate IO-108 as monotherapy and in combination with anti-PD-1 –

PALO ALTO, Calif.–(BUSINESS WIRE)–#cancer–Immune-Onc Therapeutics, Inc. (“Immune-Onc”), a clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting immunosuppressive myeloid checkpoints, today announced that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for IO-108, a novel antagonist antibody targeting Leukocyte Immunoglobulin-Like Receptor B2 (LILRB2, also known as ILT4) for the treatment of solid tumors. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer’s annual meeting demonstrate that IO-108 functions as a myeloid checkpoint inhibitor. IO-108 reprograms immune-suppressive myeloid cells toward a pro-inflammatory phenotype, leading to enhanced innate and adaptive anti-tumor immunity.

“The clearance of the IO-108 IND represents another major milestone for Immune-Onc as we progress our pipeline of novel myeloid checkpoint inhibitors targeting the LILRB family of immune inhibitory receptors,” said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. “We are highly encouraged by the strength of the preclinical data of IO-108 and are pleased that our expertise in LILRB biology and translational sciences enables us to advance this asset into the clinic. We look forward to initiating the trial to further understand the role of LILRBs in cancer, and to test the potential of IO-108 in treating patients with advanced solid tumors.”

The Phase 1, multicenter, dose-escalation study will consist of a monotherapy cohort and a combination therapy cohort to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of IO-108 alone and in combination with pembrolizumab, an anti-PD-1 antibody. Biomarkers will be assessed to enable a mechanistic understanding of clinical data and inform future trials. This study may also provide an opportunity to identify preliminary efficacy signals. After determination of the recommended Phase 2 dose, Immune-Onc plans to evaluate the efficacy, safety, and tolerability of IO-108 in combination with pembrolizumab and as monotherapy in indication-specific expansion cohorts.

IO-108 binds to LILRB2 with high affinity and specificity and blocks the interaction of LILRB2 with multiple ligands that are involved in cancer-associated immune suppression including HLA-G, ANGPTLs, SEMA4A, and CD1d. In preclinical studies, treatment of various primary human immune cell systems containing myeloid cells with IO-108 results in enhanced pro-inflammatory responses to multiple stimuli that are relevant to anti-tumor immunity. As a single agent, IO-108 reverses the anti-inflammatory myeloid cell phenotype that results from “tumor conditioning” and promotes the differentiation of monocytes into pro-inflammatory dendritic cells. Moreover, IO-108 potentiates the effect of PD-1 blocking antibodies on CD4⁺ T cell activation in co-cultures with allogeneic macrophages. In mouse models IO-108 inhibits the growth of solid tumors, which is associated with enhanced T cell responses. Together these data demonstrate that IO-108 has the potential to provide additive or synergistic benefit in combination with standard-of-care immunotherapies and/or immunogenic therapies for solid tumors that are both resistant and sensitive to T-cell checkpoint inhibitors.

ABOUT LILRB2 (ILT4)

LILRB2, also known as ILT4, is expressed mostly on myeloid cells, including monocytes, dendritic cells, macrophages, and neutrophils. In solid tumors, interaction of LILRB2 with tumor microenvironment (TME) relevant ligands, including HLA-G, ANGPTLs, SEMA4A, and CD1d, makes myeloid cells pro-tumorigenic (tolerating or promoting tumor growth) and promotes tumor immune evasion.

ABOUT IMMUNE-ONC THERAPEUTICS, INC.

Immune-Onc Therapeutics, Inc. (“Immune-Onc”) is a clinical-stage cancer immunotherapy company dedicated to the discovery and development of novel myeloid checkpoint inhibitors for cancer patients. The company aims to translate unique scientific insights in myeloid cell biology and immune inhibitory receptors to discover and develop first-in-class biotherapeutics that disarm immune suppression in the tumor microenvironment.

Immune-Onc has a promising pipeline with a current focus on targeting the Leukocyte Immunoglobulin-Like Receptor subfamily B (LILRB) of myeloid checkpoints. Immune-Onc’s focused platform approach has led to the development of several promising therapeutics across various stages of development, including IO-108 in Phase 1 clinical development for solid tumors and IO-202, a first-in-class antibody targeting LILRB4 (also known as ILT3), in Phase 1 clinical development for the treatment of acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML). The company also plans to evaluate IO-202 in solid tumors. The U.S. Food and Drug Administration granted IO-202 Orphan Drug Designation for treatment of AML in October 2020. Additional assets in Immune-Onc’s pipeline include IO-106, a first-in-class anti-LAIR1 antibody, and multiple undisclosed programs for solid tumors and hematologic malignancies.

The company has strategic research collaborations with The University of Texas, Albert Einstein College of Medicine, and Memorial Sloan Kettering Cancer Center, and has invested in proprietary models, assays, and tools to interrogate the biology and translate this cutting-edge research into the development of novel therapies. Headquartered in Palo Alto, California, Immune-Onc has assembled a diverse team with deep expertise in drug development and proven track records of success at leading biotechnology companies. For more information, please visit www.immune-onc.com and follow us on Twitter and LinkedIn.

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Tara Cooper

The Grace Communication Group

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