N17350 is designed to use the injected tumor as the source of a personalized immune response, without requiring tumor sequencing or custom manufacturing
Initial data show no dose-limiting toxicities in three heavily pretreated patients and five non-injected lesions becoming undetectable on imaging in a patient with Merkel cell carcinoma at the starting dose
SAN DIEGO--(BUSINESS WIRE)--#ELANE--Onchilles Pharma, a clinical-stage biotechnology company pioneering next-generation cancer therapeutics that harness the ELANE pathway, today announced preliminary clinical findings from OP-NEU-101, its Phase 1/2 trial of intratumoral N17350 in patients with advanced solid tumors. Derived from a cancer-killing enzyme present in human neutrophils, N17350 is designed to use the injected tumor as a source of antigens that may help train the immune system to attack cancer elsewhere in the body without the need for tumor sequencing, antigen selection, or custom manufacturing. The findings provide an early clinical test of this approach and will be presented at the 41st Annual Meeting of the Society for Immunotherapy of Cancer (SITC).
“Many personalized cancer immunotherapies today require sequencing each tumor and manufacturing a product for each patient. N17350 is designed to generate a personalized immune response with one medicine, using the tumor itself as the source,” said Court R. Turner, J.D., Co-Founder and CEO of Onchilles Pharma. “If the local and distant activity seen throughout our preclinical work can be reproduced in patients, N17350 could generate a response tailored to each patient’s cancer across many solid tumor types.”
N17350 builds on breakthrough research published in Cell showing that neutrophils, among the body’s most abundant immune cells, contain an enzyme that can kill cancer cells while sparing healthy tissue, including immune cells. Onchilles engineered that enzyme into an investigational therapy to work in two stages when N17350 is injected into the tumor: 1) selectively kill cancer cells and 2) release the tumor’s own antigens to train the immune system, helping it find and attack disease elsewhere in the body. By targeting a vulnerability shared across many cancers, N17350 is designed to generate a personalized immune response from each patient’s injected tumor without requiring a custom-made or targeted therapy.
“Many intratumoral therapies, including TLR agonists and oncolytic viruses, have shown promise preclinically but failed to demonstrate broad clinical benefit,” said Alain Patrick Algazi, M.D., Professor of Clinical Medicine at the University of California San Francisco (UCSF) and presenting author. “The early data from N17350 suggest it may be meaningfully different, with evidence of systemic immune activation and response beyond the injected lesion. If confirmed, this could represent a genuine advance over prior approaches in this space.”
The clearest early evidence of activity came from a patient with Merkel cell carcinoma, a rare and aggressive skin cancer that had continued to progress despite avelumab-based treatments and radiotherapy. N17350 was injected into one of six lesions included in the assessment. At Week 8, the investigator’s RECIST 1.1 assessment found that all five non-injected lesions were no longer detectable. These included one lesion selected for precise measurement on scans and four additional lesions being followed for their presence or absence. FDG-PET imaging showed a 56% to 60% reduction in SUVmax across all lesion groups evaluated, reflecting substantially lower uptake of the radioactive glucose tracer used to measure tumor metabolic activity. An independent radiology review of a separate lesion also found reduced FDG uptake, providing a second assessment consistent with activity beyond the injected tumor.
“Seeing all five non-injected lesions become undetectable after treating a single lesion with N17350 is an encouraging early observation, particularly after this aggressive cancer had progressed on prior immunotherapy,” said Professor Matteo Carlino, MBBS, Ph.D., FRACP, medical oncologist at Westmead and Blacktown Hospitals and an investigator on the OP-NEU-101 clinical trial. “If confirmed and repeated, this could show that N17350 can turn one treated tumor into an in situ vaccine and mobilize the immune system against cancer throughout the body.”
Across the first dose cohort, three heavily pretreated patients received N17350 at 1 mg/mL and completed the dose-limiting toxicity assessment period with no dose-limiting toxicities, supporting progression to the next dose level. Preliminary pharmacokinetic (PK) analysis detected no active N17350 enzyme in plasma at any sampled time point, and no treatment-emergent anti-drug antibodies were detected, consistent with the preclinical PK data. Initial immune profiling in the Merkel cell carcinoma patient showed a shift toward an effector-dominant, less immunosuppressive immune profile. Together, the pharmacokinetic and immune findings suggest that treatment of one tumor may have triggered an immune response that contributed to the activity in the non-injected lesions, rather than active N17350 reaching those tumors through the bloodstream.
SITC 2026 Presentation Details for N17350
- Poster: 544
- Title: OP-NEU-101: A Phase 1/2 Open-Label, Dose Finding and Expansion Study to Investigate the Safety and Effectiveness and Determine the Optimal Dose of N17350 Administered Intratumorally in Participants With Advanced Solid Tumors
- Presenting Author: Alain Patrick Algazi, MD, University of California San Francisco
- Date: Saturday, November 7
- Presentation Hours: 12:15–1:45 p.m. and 6:40–8:10 p.m. MT
- Location: Phoenix Convention Center, North Building, Lower Level, Exhibition Halls 4–6
About N17350
N17350 is a first-in-class, clinical-stage engineered therapeutic elastase designed for intratumoral administration. It targets the ELANE pathway, a cancer-selective killing mechanism that exploits altered histone H1 biology, a vulnerability shared across diverse cancers. By inducing immunogenic cancer cell death while largely preserving non-cancer and immune cells, N17350 is designed to deliver two complementary waves of activity: rapid, direct tumor killing and an adaptive immune response with the potential to attack tumors beyond the injection site. In preclinical models, N17350 produced broad, genotype-independent tumor regression, CD8+ T cell-mediated antitumor immunity, activity in non-injected tumors, and immune memory.
About OP-NEU-101
OP-NEU-101 (ClinicalTrials.gov Identifier: NCT07339176) is a Phase 1/2, first-in-human, multicenter, open-label study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary clinical activity of intratumoral N17350 in patients with advanced solid tumors. The study is enrolling in Australia and the United States, with dose escalation and optimization in patients with injectable superficial lesions, followed by planned evaluation in visceral lesions and potential indication-specific expansion cohorts.
About Onchilles Pharma
Onchilles Pharma is a clinical-stage biotechnology company pioneering first-in-class cytotoxic therapies designed to selectively kill cancer cells while preserving and activating immune function. By harnessing the ELANE pathway, these next-generation therapeutics are designed to deliver potent and selective tumor cell destruction, overcoming the limitations of traditional chemotherapy and immunotherapy. The company’s pipeline includes N17350, a tumor-directed lead candidate in first-in-human studies, and the NEU-002 program extending ELANE pathway therapeutics to systemic delivery. For more information, visit www.onchillespharma.com.
Contacts
Company: Peter Haberz, Ph.D., Vice President, Corporate Development, info@onchillespharma.com
Media: Jessica Yingling, Ph.D., Little Dog Communications Inc., jessica@litldog.com
