Development of a Novel Immunotherapeutic for Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) and the Need for Advanced Treatment: AML is a prevalent hematological
malignancy in adults, with a 5-year survival rate of only 32%. While approximately 32,000 AML patients are
diagnosed annually in the US today, projections suggest this will rise to 36,000 by 2027. Current treatments,
such as allogeneic bone marrow transplantation, have limited applicability due to high morbidity and treatment-
associated mortality.
The Problem of Immune Evasion: AML cells employ immune evasion tactics, notably up-regulation of co-
inhibitory ligands like Vasoactive Intestinal Peptide (VIP), which results in exhausted and non-functional T cells,
thwarting an effective anti-cancer response. Current immune check-point therapies using anti-PD1 and anti-PD-
L1 antibodies are ineffective in AML patients.
Solution - Development of ANT308-Fc3 Fusion: Cambium Oncology is a biotech start-up developing novel
immunotherapeutic drugs to treat cancer. Cambium Oncology’s research indicates that roughly 30% of AML
cells over-express VIP, which dampens T-cell activation. Cambium Oncology has a worldwide exclusive license
to patents covering VIP-receptor antagonists from Emory University. A peptide-based VIP-receptor antagonist,
VIPhyb, showed promise in pre-clinical studies but had a limited potency and a short half-life. Cambium Oncology
used in silico screens and in vivo testing to identify a novel VIP-receptor antagonist, ANT308, which, when fused
to the Fc region of the IgG protein, became ANT308-Fc3 fusion, Cambium Oncology’s lead candidate drug.
ANT308-Fc3 fusion exhibits enhanced potency against pre-clinical mouse models of AML with both high and low
levels of VIP expression. The work's future impact is increased by applying this approach to other cancers.
SBIR Phase 1 & 2 Objectives: Phase 1 will determine ANT308-Fc3 fusion's potency in human T cell activation
(Aim 1), its anti-leukemia activity in mice (Aim 2), and its stability and pharmacokinetics (Aim 3). Phase 2 will
focus on in vivo toxicology (Aims 4 & 5) and pharmacodynamic studies to identify responsive biomarkers for
clinical trials (Aim 6). The SBIR fast-track proposal aims to develop an IND package to submit to the FDA
supporting a phase 1 clinical trial of ANT308-Fc3 fusion in AML. The SBIR team is experienced in anti-cancer
immunology and drug development and is led by Dr. Gary Altman, Ph.D., a business executive with experience
in biotech start-ups and obtaining FDA approval for IND pharmaceuticals. The proposed project aims to advance
ANT308-Fc3 fusion as a first-in-class immunotherapy to enhance treatment outcomes for AML patients.

Grant Number: 4R44CA285206-02
NIH Institute/Center: NIH
Principal Investigator: Gary Altman