ONM-501 demonstrates enhanced tumor retention with a favorable nonclinical safety profile

The ON-BOARD™ platform demonstrates enhanced therapeutic indices with tumor specific delivery of a bispecific antibody and a cytokine

SOUTHLAKE, TX, USA I April 18, 2023 IOncoNano Medicine, Inc. presented three posters at the American Association for Cancer Research (AACR) Annual Meeting 2023. The posters detail positive nonclinical data for ONM-501, the Company’s dual-activating STING (STimulator of INterferon Genes) agonist and lead therapeutic development candidate, formulated with the company’s OMNI™ polymer technology as well as positive data for encapsulated bispecific antibody and cytokine using ON-BOARD™ tumor specific delivery technology.

“STING plays a critical role in innate immune response against infection and cancer, and we continue to be pleased with the data which support further advancement of the ONM-501 program,” said Ruolan Han, Ph.D., Vice President of Nonclinical & Translational Medicine for OncoNano Medicine. “We look forward to bringing ONM-501 to the clinic this year and furthering the development of OMNI™ as we work toward our goal of delivering critical treatments to patients in need. Previous preclinical studies have shown that ONM-501 works by stabilizing the STING protein and delivering cGAMP intracellularly, where it is shielded from degradation by ectonucleotide pyrophosphatase/phosphodiesterase 1(ENPP1). Combining these observations and the immune stimulation with limited systemic toxicity observed in the nonclinical species, we believe that ONM-501 has the potential to show an improved clinical profile as compared to earlier experimental STING agonists.”

Previously, ONM-501, a dual-activating STING agonist, has demonstrated the ability to produce a burst and sustained activation of STING signaling that leads to a robust adaptive immune response through a unique polymer-STING binding mechanism which differs from earlier cyclic di-nucleotide (CDN) STING agonist programs. This novel mechanism provides potent anti-tumor efficacy as a monotherapy and in combination with anti-PD1 in multiple preclinical mouse models with both “hot” and “cold” tumor microenvironments. In vivo pharmacodynamic (PD) analysis confirmed STING activation, enhanced tumor lymphocyte infiltration, and tumor PD-L1 upregulation by ONM-501 and demonstrated the target-engagement activity of ONM-501 in multiple species. New pharmacokinetics/biodistribution data presented at the conference in tumor-bearing mice revealed that intratumorally injected ONM-501 showed high tumor retention and very low systemic exposure due to the polymeric micelle formulation, maximizing antitumor efficacy while minimizing systemic toxicity. This new data further differentiates ONM-501 from other small molecule STING agonist programs. Safety studies in multiple species established a wide therapeutic window for ONM-501 making it a promising candidate for clinical evaluation.

Two additional posters were presented earlier in the conference, reporting encapsulation and masked delivery of Interleukin-12 (IL-12) and T cell engager bispecific antibodies using ON-BOARD™. The results demonstrate significantly improved tolerability, anti-tumor efficacy in mice and potential for clinical translation.

“Our ON-BOARD™ pH-sensitive micelle delivery platform continues to demonstrate improvement of therapeutic indices with a variety of therapeutic protein payloads including the highly potent interleukin-12 and T-cell engagers,” said Tian Zhao, Ph.D., Vice President of Research and Development for OncoNano Medicine. “We have seen challenges with other IL-12 and T-cell engager programs related to suboptimal therapeutic index, associated with toxicities related to systemic exposure. In contrast, the tumor-specific delivery of ON-BOARD™ encapsulated molecules demonstrates a much broader therapeutic window. The promising data that we presented at AACR 2023 suggest our technology may provide a solution to overcome the clinical application limitations of these highly potent protein therapeutics.”

Presentation Overview:
TITLE:   Improved tolerability and tumor specific delivery of a therapeutic bispecific T cell engager using a pH-sensitive nanoparticle platform
PRESENTER:   Qingtai Su, Ph.D.
TITLE:   Encapsulation of IL-12 with an ultra pH-sensitive nanoparticle platform improves tolerability and promotes antitumor response in mice
PRESENTER:   Tian Zhao, Ph.D.
TITLE:   ONM-501, a dual-activating polyvalent STING agonist, enhances tumor retention and demonstrates favorable preclinical safety profile
PRESENTER:   Zirong Chen, Ph.D.

About OncoNano Medicine 
OncoNano Medicine is developing a new class of products that utilize principles of molecular cooperativity in their design to exploit pH as a biomarker to diagnose and treat cancer with high specificity. Our product candidates and interventions are designed to help patients across the continuum of cancer care and include solid tumor therapeutics, agents for real-time image guided surgery and a platform of immuno-oncology therapeutics that activate and guide the body’s immune system to target cancer.

OncoNano’s lead development candidate is pegsitacianine, a novel fluorescent nanoprobe using the ONBOARD platform, that is currently under study in Phase 2 clinical trials as a real-time surgical imaging agent for use in multiple cancer surgeries. ONM-501, OncoNano’s second development program, is a next generation STING (STimulator of INterferon Genes) agonist that is advancing towards a first in human trial in the first half of 2023. Pegsitacianine and ONM-501 have been supported by grants received from the Cancer Prevention Research Institute of Texas. Learn more at www.OncoNano.com.

SOURCE: OncoNano Medicine