On April 14, 2023 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a private, clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting myeloid checkpoints, reported encouraging Phase 1 dose escalation data for IO-108, a novel myeloid checkpoint inhibitor targeting Leukocyte Immunoglobulin-Like Receptor B2 (LILRB2, also known as ILT4) (Press release, Immune-Onc Therapeutics, APR 14, 2023, View Source [SID1234630101]). The data will be presented in an oral session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Orlando, Florida, April 18. Preclinical data for IO-312, a novel bispecific antibody targeting LILRB4 (ILT3) and CD3 (LILRB4 x CD3) will also be presented on April 18 as a late-breaking poster at AACR (Free AACR Whitepaper) 2023.

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We have great news to share this year at #AACR23! Data from our Ph 1 study show encouraging clinical benefit for IO-108 as a monotherapy & when combined with pembrolizumab. Don’t miss the oral presentation on Tue., April 18 at 4:05-4:15 PM ET (CT040)

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"We are very encouraged to see promising signs of clinical activity across multiple solid tumor types and a favorable safety profile with our first-in-class myeloid checkpoint inhibitor, IO-108," said Charlene Liao, Ph.D., chief executive officer and board chair of Immune-Onc. "Our data demonstrates the utility of IO-108 as a new therapeutic modality to address key unmet needs for patients with solid tumors that do not respond to, develop resistance to, or relapse following, treatment with T cell checkpoint inhibitors."

The Phase 1 dose escalation study of IO-108 is intended to evaluate primary objectives of safety and tolerability, and secondary and exploratory objectives of pharmacokinetics, immunogenicity, pharmacodynamic (PD) biomarker effects, and antitumor activity of IO-108 as a monotherapy and in combination with pembrolizumab in patients with advanced solid tumors. The trial enrolled 25 advanced cancer patients with relapsed/refractory solid tumors. Patients received escalating doses of IO-108 (60 mg -1800 mg) intravenously once every three weeks (Q3W). Treatment with IO-108 was well-tolerated to the maximum administered dose (1800 mg Q3W); the maximum tolerated dose was not reached. Among 23 evaluable patients (11 monotherapy, 12 combination therapy plus 1 crossover), results showed 1 complete response and 4 stable disease patients in the monotherapy cohorts and 3 partial responses and 4 stable disease patients in the combination cohorts.

The 4 responding patients remain on study with an ongoing treatment duration of 8 to 12+ months as of abstract submission. Clinical benefit correlated with baseline characteristics and post-treatment changes in PD biomarkers including reprogramming of myeloid cells and activation of T cells.

"Treating patients who are refractory to treatment with T-cell immune checkpoint inhibitors remains an ongoing challenge across many tumor types," said IO-108 Phase 1 investigator, Matthew H. Taylor, M.D., Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon. "I am very encouraged by these results, particularly the complete response to IO-108 monotherapy treatment in the Merkel cell carcinoma patient who had progressed on prior anti-PD-1 treatments. These findings suggest that LILRB2 is a critically important immunotherapy target."

The initial data from dose escalation supports further development of IO-108. The preliminary recommended Phase 2 dose (RP2D) is 1200 mg Q3W which is projected to achieve full receptor occupancy in at least 90% of patients. The ongoing IO-108 Phase 1 study is actively enrolling several biomarker-driven dose expansion cohorts, using IO-108 at RP2D as a monotherapy and in combination with anti-PD-1 antibodies (pembrolizumab, cemiplimab or tislelizumab), both in the U.S. and China.

Immune-Onc oral and poster presentation details are as follows:

Abstract Number: 9498
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: Dose escalation study
Presenter: Matthew H. Taylor, M.D., Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon
Session Title: Novel Immunotherapy Combination Clinical Trials
Session Date and Time: Tuesday, April 18, 2:30 p.m. – 4:30 p.m. ET
Presentation Number: CT040

Abstract Number: LB217
Title: A novel bispecific LILRB4/CD3 antibody with potent killing of monocytic acute myeloid leukemia cells
Presenter: Charlene Liao, Ph.D., chief executive officer of Immune-Onc Therapeutics, Inc.
Session Title: Late-Breaking Research: Immunology 2
Session Date and Time: Tuesday, April 18, 9:00 a.m. – 12:30 p.m. ET
Location: Poster Section 36, Poster Board #10

Abstracts and full session details can be accessed through the AACR (Free AACR Whitepaper) Online Program Planner

ABOUT IO-108

IO-108 is a fully human IgG4 monoclonal antibody with high affinity and specificity towards LILRB2 (also known as ILT4). It blocks the interaction of LILRB2 with multiple ligands that are involved in cancer-associated immune suppression, including HLA-G, ANGPTLs, SEMA4A and CD1d. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting and the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting demonstrate that IO-108 functions as a myeloid checkpoint inhibitor and promotes innate and adaptive anti-cancer immunity.

The ongoing Phase 1 study of IO-108 in adult cancer patients has completed dose escalation in the U.S. (NCT05054348) and is actively enrolling several expansion cohorts, as a monotherapy and in combination with anti-PD-1 antibodies (pembrolizumab, cemiplimab or tislelizumab), both in the U.S. and China. To date, IO-108 has been well tolerated with demonstrated clinical activity in multiple tumor types, both as a monotherapy and in combination with pembrolizumab.