- N17350 is the first drug candidate from Onchilles’ platform that is based on the breakthrough discovery of a novel mechanism of action inspired by the immunobiology of neutrophils, which activates cell death pathways specific to cancer cells
- Presented preclinical data show that N17350 broadly and selectively kills cancer cells, stimulates robust adaptive and innate immune responses, and does not induce resistance after repeated treatments
- In 2024 Onchilles plans to initiate first-in-human clinical trials to evaluate N17350 in non-melanoma skin cancer, head and neck cancer, and triple-negative breast cancer
SAN DIEGO and ORLANDO, April 19, 2023 – Onchilles Pharma, a private biotech company developing novel cancer therapeutics that leverage myeloid biology, presented new preclinical data on N17350, a first-in-class biologic therapeutic inspired by ELANE, a protein found in neutrophils that is part of a newly discovered innate cancer-killing pathway. The data demonstrate N17350, as a monotherapy or in combination with checkpoint inhibitors, abrogates tumor growth, induces a robust immune signature with the potential to establish durable remission, and demonstrates no acquired resistance. These data were presented at the American Association for Cancer Research (AACR) Annual Meeting 2023 taking place in Orlando.
“While significant therapeutic innovation has occurred in immuno-oncology, it’s clear that we need to continue to explore new treatment paradigms that can selectively kill tumors and yield durable therapeutic responses. When we discovered the ELANE pathway, we saw the potential for a novel approach in immuno-oncology that combines broad activity in cancer cells but not in normal cells, robust immune system activation with immunological memory, and an inability to develop resistance,” said Lev Becker, Ph.D., Scientific Founder and Board Member of Onchilles Pharma. “N17350 was specifically designed to mobilize the ELANE-mediated cancer-killing pathway, and in addition to its potent single agent activity, we believe it could enhance most immunotherapies, lead to global responses, and represent a new treatment modality in immuno-oncology.”
Data presented at AACR show that in the CT26 tumor model, a single dose of N17350 abrogated tumor growth, maintained tumor-free status upon 90-day rechallenge with no observed toxicity, and enhanced survival compared to standard of care chemotherapy. Also presented were data from the 4T1 tumor model, where a single dose of N17350 demonstrated tumor regression and an abscopal effect driven by CD8+ T cells to control lung metastases. Furthermore, in the 4T1 model, N17350 in combination with anti-CTLA4 antibody treatment, demonstrated the potential to enable immune checkpoint inhibitor efficacy in an immunologically “cold” tumor model.
“We have generated a substantial amount of preclinical data demonstrating N17350 is unlike any other immuno-oncology therapeutic approach,” Court R. Turner J.D., Co-Founder & Executive Chair of Onchilles Pharma. “These data compel us to move N17350 into the clinic to help patients with limited treatment options.”
Click here to download the poster.
About N17350 and the ELANE Pathway
First described in research published in Cell from the lab of Onchilles’ Co-Founder Lev Becker, human neutrophils release catalytically active neutrophil elastase, called ELANE, which initiates a complex killing mechanism that culminates in cancer cell apoptosis at the initial tumor site as well as increases adaptive immunity that attacks distant metastases. ELANE selectively kills cancer cells by proteolytically liberating the CD95 death domain, which interacts with histone H1. This starts a complex cell death program only active in cancer cells that suppresses cell survival pathways, induces DNA damage, elevates mitochondrial reactive oxygen species production, and ultimately activates apoptosis effectors. The team at Onchilles translated the ground-breaking scientific discovery of ELANE, into a proprietary set of molecules including N17350, that mobilize the ELANE-mediated cancer-killing pathway and have the potential to treat a wide variety of tumor types with an optimal safety and efficacy profile.
About Onchilles Pharma
Onchilles Pharma translates breakthrough research in novel innate immune biology into first-in-class therapeutics designed to selectively kill tumors and promote a systemic immune response. The company is developing a pipeline of first-in-class drug candidates based on novel druggable pathways that have the potential to be broadly effective against a wide range of cancers. Onchilles is headquartered at the Alexandria GradLabs in San Diego.
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