OncoNano Medicine Presents Preclinical Data for ON-BOARDtm IL-12 Program at AACR Annual Meeting 2024

OncoNano Medicine, Inc. presented a late-breaking poster detailing the preclinical efficacy and safety of muONM-412, an ON-BOARDtm nanoparticle-encapsulated murine interleukin-12 fusion protein (IL-12Fc), and in vitro characterization of ONM-412, encapsulating human IL-12Fc, at the American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego, California.

Despite its potent pleiotropic and well-established anti-cancer effects, the clinical application of IL-12 has been hindered by significant adverse toxicities. OncoNano developed ON-BOARDtm, an ultra-pH sensitive nanoparticle platform, to shield payloads from systemic exposure and target solid tumors by responding to the highly acidic tumor microenvironment. Encapsulation of payloads like IL-12 by ON-BOARDtm may provide the opportunity to improve the therapeutic index of a variety of anti-cancer therapies.

"As part of the study presented at AACR, the preclinical safety and activity of muONM-412 were evaluated with the data demonstrating it significantly improved tolerability over unencapsulated IL-12Fc while showing potent antitumor efficacy in mice. Findings also reveal that ONM-412 illustrates favorable stability and pH-responsive IL-12 bioactivity in vitro," said Tian Zhao, Ph.D., Vice President of Research and Development for OncoNano Medicine. "We believe our ON-BOARDtm ultra-pH sensitive micelle technology can transform the targeted delivery of oncology therapeutics and look forward to continuing the development of new treatments for patients with cancer."

muONM-412 key findings:

• Exhibited improved tolerability in vivo compared to unencapsulated IL-12Fc through the observation of reduced body weight loss, absence of liver toxicity and lower plasma IFNy levels.
• Induced tumor immune remodeling, with increased infiltration by IFN?+ and GzmB+ CD8 T and NK cells.
• Strong dose-responsive anti-tumor efficacy shown in MC38 tumor-bearing animals.

ONM-412 key findings:

• Demonstrated high encapsulation efficiency (>85%) in uniformly distributed particles (Dh<50nm) with 12-month on-going shelf-life stability.
• Rapid and complete recovery of IL-12 bioactivity shown <10 minutes after acid-activation.
• Confirmed pH-specific release in vitro with a >100-fold activation window between the acid-activated and intact formulations by a HEK reporter assay and an IFN? induction assay.

Presentation Overview:

TITLE: Preclinical characterization of ONM-412, an ultra-pH sensitive nanoparticle encapsulated IL-12 fusion protein
PRESENTER: Jason Miller, Ph.D., Associate Director, Research Pipeline Development, OncoNano Medicine

Link to the poster may be found on the OncoNano Medicine website at: News - OncoNano Medicine.

About OncoNano Medicine

OncoNano Medicine is developing a new class of cancer therapeutics that exploit pH to diagnose and treat solid tumors with high specificity. OncoNano's ON-BOARDtm platform is generating a robust oncology pipeline to support novel therapeutic development for patients with high unmet medical needs. 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 including 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 currently in phase 1 studies. ONM-412, the highly potent pro-inflammatory cytokine, interleukin-12 (IL-12), encapsulated in the ON-BOARDtm ultra-pH sensitive micelle system is currently in preclinical development along with other novel targets. Additionally, the ON-BOARDtm platform has been used for pegsitacianine, a 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. The work of OncoNano is supported through grants from the Cancer Prevention & Research Institute of Texas. Learn more about OncoNano's platform and pipeline at www.OncoNano.com.