On February 1, 2021 Kadmon Holdings, Inc. (NASDAQ:KDMN) reported the publication of preclinical data demonstrating that KD033, the Company’s anti-PD-L1/IL-15 fusion protein, achieved robust anti-tumor responses in multiple syngeneic tumor models (Press release, Kadmon, FEB 1, 2021, View Source [SID1234574464]). The data were published in Molecular Cancer Therapeutics, an American Association for Cancer Research (AACR) (Free AACR Whitepaper) journal. KD033 is currently being evaluated in a Phase 1 study in patients with metastatic or locally advanced solid tumors.

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"These preclinical data demonstrate the ability of KD033 to produce meaningful efficacy and generate a memory response in a variety of tumors after a single dose," said Harlan W. Waksal, M.D., President and CEO of Kadmon. "The biological activity and safety shown to date further reinforce the potential of KD033 to stimulate innate and adaptive immune responses in patients with metastatic or locally advanced solid tumors."

KD033 is an antibody-cytokine fusion protein harnessing the immunostimulatory activity of IL-15. The IL-15 cytokine expands key tumor-fighting immune cells, including natural killer (NK), NKT and memory CD8 cells, to induce long-lasting responses. Importantly, IL-15 does not expand immunosuppressive Treg CD4 cells, allowing for a robust and durable anti-tumor response. With KD033, Kadmon has fused IL-15 to a PD-L1 antibody to direct IL-15 activity to the tumor microenvironment, promoting efficacy and inducing durable responses while potentially increasing tolerability.

Preclinical data published in MCT demonstrated that a single dose of KD033 inhibited tumor growth across multiple in vivo syngeneic tumor models and achieved dose-dependent efficacy in a resistant melanoma syngeneic mouse model. KD033 induced a strong immune memory response with a single treatment, resulting in mice that remained tumor-free following several tumor re-challenges. Furthermore, KD033 in combination with anti-PD1 therapy demonstrated synergistic activity, providing rationale for administering KD033 in combination with other immune checkpoint inhibitors.

The manuscript, titled "Single-dose anti-PD-L1/IL-15 fusion protein KD033 generates synergistic anti-tumor immunity with robust tumor-immune gene signatures and memory responses," is now available online preprint at View Source and will be published in the journal’s February 2021 issue.

About the KD033-101 Clinical Trial

KD033-101 is a Phase 1, open-label, dose-escalation and dose-expansion study investigating the safety and efficacy of KD033 in patients with metastatic or locally advanced solid tumors. The dose-escalation phase of the study will evaluate the pharmacokinetics and pharmacodynamics and identify the maximum tolerated dose (MTD) of KD033. The dose-expansion phase of the study will enroll approximately 15 patients who have progressed or are refractory to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor therapy to assess safety, efficacy and determine the recommended Phase 2 dose (RP2D) of KD033.

About KD033

KD033 is a novel immunotherapy developed in-house and is fully owned by Kadmon. KD033 combines an anti-PD-L1 antibody with IL-15, a cytokine that expands key tumor-fighting cell types, including natural killer (NK), natural killer T (NKT) and memory T cells, to potentially induce durable responses and inhibit tumor growth. The anti-PD-L1 antibody directs IL-15 activity to the tumor microenvironment, limiting systemic exposure of IL-15 to potentially increase safety and tolerability. KD033 was well tolerated in GLP toxicology studies at clinically relevant doses. KD033 process development and manufacturing was completed through a successful collaboration with Wuxi Biologics and exhibited desired manufacturability and stability criteria.

KD033 is the most advanced candidate from Kadmon’s IL-15 fusion protein platform. The Company is developing a portfolio of therapies combining IL-15 with select antibodies for the treatment of cancer.