# Non-clinical Combination Pharmacology Studies and Phase 1 Clinical Development of IO-202 in Acute Myeloid Leukemia (AML)

> **NIH NIH R44** · IMMUNE-ONC THERAPEUTICS, INC. · 2020 · $1,070,000

## Abstract

Abstract
In this Direct-to-Phase 2 SBIR, Immune-Onc Therapeutics proposes development of IO-202, a safe and active
therapy for prolonging the survival of patients with monocytic acute myeloid leukemia (AML) and chronic
myelomonocytic leukemia (CMML). AML affects 20,000 people in the US each year and has a dismal
prognosis, with a 5-year survival rate of approximately 25%. CMML is an established precursor of AML with
monocytic differentiation, with approximately 20% of CMML cases progressing to AML. Novel treatments are
urgently needed to improve patient outcomes. LILRB4 is an immune-inhibitory receptor whose expression is
restricted to normal antigen-presenting cells, where it functions as a negative regulator of immunity; it is
upregulated on monocytic subtypes of AML, where it creates an immunosuppressive micro-environment. IO-
202 is an antibody that inhibits LILRB4 signaling; LILRB4 blocking antibodies have resulted in tumor
regression, delay in tumor engraftment, and anti-leukemia T-cell activation in preclinical in vivo models of AML,
suggesting that IO-202 is a promising therapeutic candidate. The differential in expression levels between
normal and AML cells allows us to selectively target the AML cells. We hypothesize that IO-202 will block
LILRB4 signaling in leukemic cells in patients with monocytic AML, thereby activating effector T-cells, impeding
leukemic engraftment/infiltration and mediating direct leukemic cell killing through antibody-dependent cellular
cytotoxicity and antibody-dependent cellular phagocytosis. The aforementioned biological activity is
hypothesized to translate into blast count reductions in the bone marrow of patients with AML, leading to
complete remissions and prolonged survival. Here, we propose to evaluate the combination therapy of IO-202
with standard cytotoxic chemotherapy, hypomethylating agents and/or targeted therapy in non-clinical AML
models (Aim 1). In addition, we aim to characterize the safety, pharmacokinetics and activity of IO-202, an
antibody targeting LILRB4, in a first-in-human Phase 1 clinical trial in relapsed/refractory AML and CMML
patients. Data from this trial will identify the maximum-tolerated dose (MTD) of IO-202 (Aim 2) and the
recommended Phase 2 dose (RP2D) of IO-202 (Aim 3).

## Key facts

- **NIH application ID:** 10079394
- **Project number:** 1R44CA250543-01A1
- **Recipient organization:** IMMUNE-ONC THERAPEUTICS, INC.
- **Principal Investigator:** Charlene Liao
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,070,000
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10079394

## Citation

> US National Institutes of Health, RePORTER application 10079394, Non-clinical Combination Pharmacology Studies and Phase 1 Clinical Development of IO-202 in Acute Myeloid Leukemia (AML) (1R44CA250543-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10079394. Licensed CC0.

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