• The drug candidate, N17350, leverages the neutrophil elastase (ELANE) pathway, to achieve broad cancer-killing activity
• Onchilles also expanded its technology platform to generate monoclonal antibodies modulating tumor-associated macrophages (TAMs)
• The company is developing a pipeline of first-in-class biologic therapeutics to modulate the innate immune system to improve the treatment of solid tumors

Onchilles Pharma, a private biotech company developing new cancer therapeutics to modulate myeloid biology, announced today the nomination of its first drug development candidate, N17350, a first-in-class biologic therapeutic that is designed to leverage the immunobiology of neutrophils, a key part in the innate immune system, against a wide range of cancer types. The company is targeting to start first-in-human clinical trials in 2024. Onchilles also disclosed the expansion of its technology platform to design new therapeutics modulating the M2-like TAMs found in multiple solid tumor indications.

Alain P. Algazi, M.D., member of Onchilles’ Scientific Advisory Board, said, “I am extremely excited about N17350 as preclinical data shows it maintains the immune compartment while generating tumor cytotoxicity. The tumor-killing capability of N17350 yields an immunological cell death, which is a key attribute that could enhance most immunotherapies and lead to global responses.”

Research published last year in Cell from Co-Founder Lev Becker’s Lab first described a pathway where human neutrophils release catalytically active neutrophil elastase, called ELANE, to selectively kill many cancer cell types while sparing non-cancer cells. ELANE consistently activated this cancer-killing program in more than 40 different cancer cell lines but not in any non-cancer cells tested. Research shows that ELANE 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.

To advance this research into a therapeutic, Onchilles generated the N17350 molecule to mobilize the ELANE-mediated cancer-killing pathway. As part of innate immunity, neutrophils have broad efficacy and specificity to eliminate genetically diverse cellular threats. The company completed preclinical studies showing N17350 has better anti-cancer efficacy than standard of care chemotherapy in select cancer mouse models and synergy with checkpoint inhibitors in tumor models non-responsive to checkpoint blockade. Further studies have shown N17350 has an encouraging safety profile and a lack of resistance with repeated exposure.

“The team at Onchilles translated a ground-breaking scientific discovery of ELANE, the inherent cancer-killing pathway in neutrophils, into a proprietary set of molecules that have the potential to treat a wide variety of tumor types with an optimal safety and efficacy profile,” Court R. Turner J.D., Co-Founder & Executive Chair of Onchilles. “With our expanded technology platform, we are interrogating myeloid biology and generating additional molecules to leverage neutrophil biology, as well as tumor-associated macrophages, with a novel and highly differentiated approach.”

Onchilles has discovered a novel mechanism by which TAMs help tumors evade an effective adaptive immune response. Onchilles has developed proprietary antibodies for TAM targets validated on human patient samples, and these antibodies generated a more robust adaptive immune response in preclinical cancer models.

About Onchilles Pharma

Onchilles Pharma translates breakthrough research in novel innate immune biology to develop 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. For more info, visit www.onchillespharma.com.

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