ANT308 / Cambium Oncology - LARVOL DELTA

VIP pathway inhibition alters microbial metabolism to balance graft-versus-leukemia and gvhd (ASH 2025) - "ANT308 is a VIP-receptorantagonist designed to block signaling through VIP-receptors VPAC1 and VPAC2... Modulation of VIP signaling represents a promising strategy to shape gut microbialmetabolism in the context of allo-BMT. Our findings suggest that microbiome-derived metabolitesenriched through VIP pathway inhibition may contribute to improved immune balance and transplantoutcomes. Future studies will focus on defining the mechanistic roles of these metabolites and evaluatingtheir potential as therapeutic targets to enhance graft-versus-leukemia effects while mitigating GvHD."

Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia

A chronotherapeutic approach to VIP receptor antagonist (ANT308) in anti-tumor activity (ASH 2025) - "Plasma corticosterone levels reflect a strong circadian oscillation with concentrations of 3,528pg/ml at 7PM and 227 pg/ml at 7AM. VIP plasma levels did not demonstrate a significant changethroughout a 24-hour period, likely due to the short half-life of VIP in blood. However, flow cytometryanalysis of blood from tumor-bearing mice showed peak frequencies of VIP+ CD8 and CD4 T cells at 3AMwith a trough at 7PM."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Melanoma • Oncology • Solid Tumor • ARNTL • BMAL1 • CD4 • CD8 • PER2

VIP, a novel phagocytosis checkpoint in TP53-mutated Acute Myeloid Leukemia (ASH 2025) - "Corroborating secretome analysis of human leukemia cells demonstrated ahigher VIP secretion from TP53 LOF-mutated leukemia cells (HL-60 harboring homozygous deletion inTP53; Kasumi-1 with homozygous TP53-mutation, and heterozygous TP53-mutation present in CCRF-CEM) relative to control (TP53-wildtype present in THP-1). The VIP/VPAC axis functions as a previously unrecognized phagocytosis checkpoint in AML.TP53-mutation evades anti-tumor immune response via VIP. These findings support the evaluation ofANT308‑IgG4 Fc3 fusion, alone or in rational combinations, for high‑risk AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • PD-1 • TP53

Simultaneous PD-1 and VIP receptor blockade optimizes tumor immunotherapy in P815 Acute Myeloid Leukemia model (ASH 2025) - "ANT308 is a potent VIP antagonist that promotes T-cell activation anddownregulates immune checkpoint molecule expression, demonstrating single-agent anti-leukemiaactivity in murine leukemia models...The combination therapy also promoted the expansion of effector Tcell phenotypes with chemokine receptors associated with homing to tumors (CX3CR1⁺, CXCR3⁺) and anti-tumor immunity. A strategy that targets both VIP and PD-1 pathways is a promising approach toimmunotherapy in AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • CD8 • CX3CR1 • CXCR3 • HAVCR2

A VPAC1/2-targeted antagonist, preferentially binds to activated T cells and enhances T cell activation (ASH 2025) - "ANT308 binds VPAC1/2 on activated T cells, reorganizing receptors and enhancing activation markers.These findings indicate ANT308 competitively engages VIP receptors with high affinity and may effectivelycounter VIP‑mediated immunosuppression. Mechanistic studies will define ANT308-induced VPACreorganization within the membrane and downstream signaling pathways, assess competitive bindingkinetics with endogenous VIP, and test in vivo efficacy in AML and other cancers exploiting VIP signaling."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CD69 • CD8 • TINCR

Therapeutic vulnerability of prostate cancer to VPAC antagonism (PCF 2025) - "Also, enzalutamide increased phagocytosis of PC cells in VIP-knockout BMDM relative to untreated control, but not in wildtype, suggesting that VPAC1 serves as an androgen-regulated macrophage-suppressive checkpoint...In the androgen-sensitive Myc-CAP syngeneic model, a potent VIP receptor antagonist, ANT308, increased degarelix-mediated tumor control... VPAC1 is an androgen-regulated macrophage checkpoint. VPAC inhibition with ANT308 leads to anti-tumor phagocytosis and enhances ADT-mediated control of prostate tumors in both adenocarcinoma and mixed adeno-neuroendocrine diseases. Further mechanistic investigation is needed to elucidate the intrinsic versus extrinsic role of VIP/VPAC at those stages, informing the design of clinical trials for ANT308 in PC patients."

Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • AR • IL12A • MYC • SYP

Targeting the VIP-VPAC Pathway in Melanoma Models Inhibits Tumor Growth and Liver Metastasis. (PubMed, Cancer Lett) - "In vivo studies revealed that ANT308 treatment decreased MCAM expression in intraocular primary tumors, reduced the number and size of liver metastases following intraocular or subcutaneous melanoma injection, and showed a trend toward reduced tumor volume at the primary tumor site. In conclusion, our findings indicate that VIP receptor signaling promotes liver metastasis in melanoma, and targeting this pathway with VIP receptor antagonists may represent a novel therapeutic strategy for treating metastatic UVM."

Journal • Cutaneous Melanoma • Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • Uveal Melanoma • CDH2 • MCAM

TARGETING VIP-RECEPTOR SIGNALING SELECTS A GUT MICROBIOME THAT SEPARATES GRAFT-VERSUS-LEUKEMIA (GVL) FROM GRAFT-VERSUS-HOST DISEASE (GVHD) IN ALLOGENEIC BONE MARROW TRANSPLANTATION (ALLO-BMT) (EBMT 2025) - "A potent peptide VIP-receptor antagonist (ANT308) was administered daily via subcutaneous injection for four weeks pre-transplant and/or four weeks post-transplant to evaluate its impact on microbiome composition and transplant outcomes... Microbiome transfer from VIP-KO mice to WT mice enhances anti-leukemic immunity, demonstrating the potential of a VIP-deficient microbiome to bolster tumor control. Pharmacologic inhibition of VIP signaling promotes microbiome shifts that mitigate GvHD while preserving GvL effects. These findings identify VIP-receptor signaling modulation as a promising strategy to separate GvHD from GvL, potentially improving outcomes in allo-BMT recipients."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation

Seeking Investors: First-in-Class Immunotherapeutics for Cancer (PRNewswire) - "Cambium Oncology is pleased to share that their lead drug candidate, ANT308, recently demonstrated outstanding single-agent efficacy and safety in preclinical studies. The drug is mutation-agnostic, and the company observes no toxicity-limiting dosages. In addition to their Fast-Track SBIR NIH grant recently being funded for $2.4M, they have received a significant investment from OEP Innovations of Taiwan....MULTIPLE PROOFS-OF-CONCEPT - Leukemia and Pancreatic Cancers: (1)Leukemia: ANT308 has shown strong single-agent anti-leukemia activity in 2 mouse models. (2) Pancreatic cancer: ANT308 has shown synergistic effects with anti-PD-1 checkpoint inhibitors in 3 pancreatic cancer models."

Financing • Preclinical • Leukemia • Pancreatic Cancer

Novel Therapies for AML and other Cancers (PRNewswire) - "Cambium Oncology and Orient Euro Pharma (OEP) announce a strategic partnership in which OEP has invested $5M in Cambium Oncology. This will accelerate the clinical development of Cambium Oncology's lead therapeutic candidate, ANT308, a FIRST-IN-CLASS vasoactive intestinal peptide (VIP) receptor antagonist designed to restore anti-cancer T-cell function. This investment is in addition to $2.4M recently received from the NIH. PROOF-OF-CONCEPT: ANT308 has shown strong single-agent anti-leukemia activity in two AML mouse models and synergistic effects with anti-PD-1 checkpoint inhibitors in three pancreatic cancer (PDAC) models."

Licensing / partnership • Pancreatic Ductal Adenocarcinoma