On April 8, 2022 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a private, clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting myeloid checkpoints, reported two poster presentations on its clinical stage program IO-108, a novel myeloid checkpoint inhibitor targeting Leukocyte Immunoglobulin-Like Receptor B2 (LILRB2, also known as ILT4), at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans, Louisiana (Press release, Immune-Onc Therapeutics, APR 8, 2022, View Source [SID1234611751]).
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Tumor-associated myeloid cells are immunosuppressive cells that contribute to impaired anti-tumor responses, and limit the efficacy of currently approved cancer immunotherapies, such as T cell checkpoint inhibitors. LILRB2 is a receptor expressed primarily by myeloid cells that has several ligands known to contribute to immune suppression in the tumor microenvironment (TME).
"The pioneering work of our scientific team shows that IO-108 binds to LILRB2 with high affinity and specificity and blocks the interaction of LILRB2 with multiple immunosuppressive ligands. As a result, IO-108 activates and enhances anti-tumor immune responses ex vivo and inhibits the growth of solid tumors in preclinical models," said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. "Collectively, these studies have enabled a comprehensive clinical biomarker plan and further support the ongoing Phase 1 clinical study of IO-108 as a novel immunotherapy for multiple solid tumor types, including those that are resistant to or relapsed after T cell checkpoint inhibitor treatments."
Ex vivo studies show that treatment with IO-108 produces pro-inflammatory activity and an enhanced antigen-presenting cell (APC) phenotype to multiple stimuli, including T cell activators, and STING and TLR agonists. As a single agent, IO-108 reverts the anti-inflammatory myeloid cell phenotype caused by "tumor conditioning" to pro-inflammatory phenotype and promotes the differentiation of monocytes and immature dendritic cells into pro-inflammatory dendritic cells, which are critical in generating productive anti-tumor immune responses.
IO-108 enhances the effect of PD-1 blocking antibodies in CD4+ T cell activation by allogeneic macrophages. Moreover, IO-108 monotherapy inhibits the growth of solid tumors in a preclinical model, which is associated with immune cell activation. Importantly, IO-108 presents a favorable pharmacokinetic and safety profile in preclinical models.
In the ongoing Phase 1 study of IO-108 in adult patients with advanced or refractory solid tumors (NCT05054348), IO-108 is studied at 60, 180, 600 and 1800 mg in monotherapy and at 180, 600 and 1800 mg in combination with 200 mg of pembrolizumab, administered intravenously every three weeks. IO-108 has been well-tolerated to date, both as a monotherapy and in combination with pembrolizumab, and dose-limiting toxicity has not been observed so far, at up to 600 mg in monotherapy and 180 mg in combination with pembrolizumab. Enrollment is ongoing with the last patient in expected in the second quarter of 2022.
Details of Immune-Onc’s AACR (Free AACR Whitepaper) 2022 presentations are as follows:
Abstract Number: 601
Title: IO-108, A fully human therapeutic antibody blocking the myeloid checkpoint LILRB2/ILT4, promotes innate and adaptive anti-cancer immunity in preclinical studies
Presentation Time: April 10, 2022, 1:30 PM – 5:00 PM ET
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 38
Abstract Number: CT209
Title: A first-in-human phase 1 trial of IO-108, an antagonist antibody targeting LILRB2 (ILT4), as monotherapy and in combination with pembrolizumab in adult patients with advanced relapsed or refractory solid tumors (NCT05054348)
Presentation Time: April 12, 2022, 9:00 AM – 12:30 PM ET
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 34
ABOUT LILRB2 (ILT4)
LILRB2, also known as ILT4, is expressed mostly by myeloid cells, including monocytes, macrophages, dendritic cells, and neutrophils. In solid tumors, activation of LILRB2 by its ligands, including HLA-G, ANGPTLs, SEMA4A, and CD1d, induces a tolerogenic phenotype in myeloid cells, thereby promoting poor T cell activation and consequent tumor immune evasion.