OncoNano Medicine, Inc. today presented positive preclinical data describing the effective delivery of interleukin-12 (IL-12) with the ON-BOARDtm platform technology at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC).
The study findings show that encapsulation of a therapeutic IL-12 fusion protein (IL-12Fc) for tumor specific delivery and pH-dependent activation was achieved using the ON-BOARDtm polymeric micelle technology. The study also found that ON-BOARDtm significantly improved the tolerability of IL-12Fc, as compared to unencapsulated IL-12. The encapsulated IL-12Fc demonstrated potent anti-tumor efficacy and durable anti-tumor memory in the MC38 colorectal cancer model. ONM-412, the development product candidate with the IL-12 encapsulated in the ON-BOARDtm polymeric micelle system, is advancing through IND-enabling activities.
"These findings underscore the potential application of the ON-BOARDtm polymeric micelle system for the delivery of IL-12 as an anti-tumor agent," said Tian Zhao, PhD, Vice President of Research and Development at OncoNano. "We look forward to the continued development of ONM-412 and the ON-BOARDtm platform as a potential technology for the targeted delivery of therapeutics to benefit cancer patients."
The data presented demonstrated that:
- ON-BOARDtm enables murine and human IL-12Fc encapsulation with favorable stability and pH-responsive IL-12 bioactivity in vitro in a HEK reporter assay and in primary cell IFN? induction. Compared to a protease cleavable masked IL-12, the ON-BOARDtm formulation shows rapid and complete activation over a short period of time.
- ON-BOARDtm encapsulated IL-12Fc exhibited potent anti-tumor efficacy and prolonged survival in MC38 tumor-bearing animals with long-term memory effect.
- ON-BOARDtm formulation demonstrated effective IL-12 signaling in the tumor as evidenced by activation of CD8 T cells and NK cells; increased levels of IFN? were seen in the tumor but not systemic circulation.
- Reduced systemic exposure was observed with ON-BOARDtm encapsulated IL-12Fc with a significant improvement in the tolerability as evidenced by reduced body weight loss, normal plasma transaminase levels for liver function, reduced splenomegaly, and reduced systemic free IL-12 levels and IL-12 related cytokines when compared to unencapsulated IL-12Fc.
Presentation Details
Title: Encapsulation of IL-12 with an ultra pH-sensitive tumor delivery platform improves tolerability and promotes antitumor response in a preclinical model
Presenter: Jason Miller, Ph.D., Associate Director, Research Pipeline Development, OncoNano Medicine
Poster Number: 1147-B
About OncoNano Medicine
OncoNano Medicine is developing a new class of cancer products that utilize principles of molecular cooperativity in their design to exploit pH as a biomarker to diagnose and treat solid tumors with high specificity. Our polymeric micelles are designed to efficiently deliver oncology payloads to the tumor microenvironment for an enhanced therapeutic index. Our product candidates and interventions are designed to help patients across the continuum of cancer care and include solid tumor therapeutics, a platform of immuno-oncology therapeutics that activate and guide the body's immune system to target cancer, and agents for real-time image guided surgery.
ONM-501, OncoNano's first therapeutic program, is a next generation dual-activating STING (STimulator of INterferon Genes) agonist that is advancing towards a first in human trial in the fourth quarter of 2023. OncoNano's second therapeutic development program is ONM-412, the highly potent pro-inflammatory cytokine, interleukin-12 (IL-12), encapsulated in the ON-BOARDtm polymeric micelle system. Additionally, the ON-BOARDtm platform has been used for pegsitacianine, a novel fluorescent nanoprobe that is being studied as a real-time surgical imaging agent for use in multiple cancer surgeries and is advancing towards a pivotal clinical trial to aid in tumor detection of peritoneal carcinomatosis. Pegsitacianine and ONM-501 have been supported by grants received from the Cancer Prevention Research Institute of Texas (CPRIT). Learn more at www.OncoNano.com.
These press releases may also interest you
|