N17350 / Onchilles Pharma - LARVOL DELTA

N17350 outperforms cytotoxic agents in killing tumors of treatment-naïve and chemotherapy-treated ovarian carcinoma patients (AACR 2025) - "In vitro tumor killing by N17350 was compared to carboplatin, paclitaxel, doxorubicin, or oxaliplatin in chemotherapy naïve and NACT patients. Our data demonstrate that, compared to standard chemotherapy, N17350 yields superior and more selective tumor killing, particularly following exposure to NACT. Tumors that are resistant to chemotherapy retain sensitivity to N17350, and N17350 could improve clinical outcomes in OvCa, including patients with chemotherapy resistant disease."

Clinical • Oncology • Ovarian Cancer • Peritoneal Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • PTPRC

Onchilles Pharma Presents New Data at AACR 2025 Highlighting N17350, a Next-Generation Cytotoxic Therapeutic Leveraging the ELANE Pathway (Businesswire) - "Highlights from the AACR Presentation Include: Broad Efficacy: N17350 was effective in killing cancer cells derived from treatment-naïve, neoadjuvant chemotherapy-treated (NACT), and recurrent ovarian tumors; Selective Cytotoxicity: While standard chemotherapies were equally toxic to both cancer and immune cells, N17350 preserved immune cell viability while inducing immunogenic cell death in cancer cells; In Vivo Superiority: In cell-derived xenograft (CDX) models from ovarian cancer patients, N17350 outperformed carboplatin in inducing tumor regression; No Resistance: N17350 maintains potency following repeat dosing and effectively kills chemotherapy-resistant cancer cells....'We remain focused on translating these compelling preclinical results into clinical benefit as we prepare to enter the clinic later this year.'"

New trial • Preclinical • Ovarian Cancer

Onchilles Expands Leadership Team to Advance First-in-Class Pan-Cancer Therapeutics Targeting the ELANE Pathway into Clinical Trials (Businesswire) - "Dr. Becker, the scientific founder of Onchilles Pharma, and his research team led the groundbreaking discovery of the ELANE pathway. As CSO, Dr. Becker will focus on advancing the company’s pipeline, which includes NEU-002, nearing development candidate status, and N17350, a tumor-directed therapy set to enter first-in-human trials in 2025."

New trial • Solid Tumor

NEU-002 leverages a cancer specific innate immune pathway to induce immunogenic cell death and stimulate anti-tumor immunity (SITC 2024) - "We previously showed that N17350, a neutrophil elastase-inspired serine protease, leverages a novel cancer-selective killing pathway1 to potently induce ICD in histone H1 rich cancer cells.2–4 This leads to complete tumor regression, regression of distant metastases, and immune memory following a single intra-tumoral injection.2–4 N17350 is rapidly inactivated by serine protease inhibitors in blood (eg. alpha-1-antitrypsin; A1AT) of mice and humans. Ethics Approval Human studies were approved by the Institutional Review Board (IRB) with protocol ID # Pro00063741(OP-NTD-01) and Pro00071913 (OP-NTD-02) for Onchilles Pharma Inc., San Diego, CA. All the animal studies were conducted as per institutional guidelines for humane animal treatment and complied with institutional animal care and use committee (IACUC) approved protocols # EB17-010-073 at CRADL vivarium, San Diego, CA."

Immunogenic cell death • Breast Cancer • Colon Cancer • Colorectal Cancer • Oncology • Ovarian Cancer • Solid Tumor • ANXA1 • CALR • CD8 • ELANE • FAS • HMGB1

N17350 kills cancer cells, spares immune cells, and regresses CDX tumors from chemotherapy naive and experienced patients (AACR 2024) - "Mice were treated with 2 doses of N17350 (400μg/100mm3, intratumoral) or carboplatin (100mg/kg, intraperitoneal), and effects on tumor growth were quantified...In contrast, doxorubicin and oxaliplatin showed similar toxicity to both cell types...Our data demonstrate that N17350 kills OvCa tumors in vitro and in vivo while sparing CD45+ immune cells in both chemotherapy naïve and experienced patients. Together with previous data showing that N17350 induces immunogenic tumor cell death, these findings suggest that N17350 could improve clinical outcomes compared to chemoimmunotherapy."

Clinical • Immune cell • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • ELANE • FAS • PTPRC

Onchilles Pharma Presents at AACR 2024 New Preclinical Data for N17350 and N17465 Demonstrating the Potential for Potent and Tumor-Selective Treatment (Businesswire) - "Onchilles Pharma...announced today the presentation of new preclinical data for...tumor-directed N17350 in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2024....N17350 killed primary cancer cells from all ovarian cancer (OvCa) patients tested but was well tolerated by non-cancer cells from the same patients; in contrast, doxorubicin and oxaliplatin showed similar toxicity to both cell types. N17350 killed cancer cells from chemotherapy-naïve and -experienced patients with equal efficacy, while doxorubicin and oxaliplatin showed less efficacy in patients previously treated with chemotherapy....N17350 mobilizes anti-tumor immunity in the 4T1 model of metastatic breast cancer and outperforms standard-of-care chemotherapy."

Preclinical • Breast Cancer • Ovarian Cancer

N17350 combines selective cancer killing with adaptive immune activation to eradicate tumors (SITC 2023) - "Conclusions Taken together, our data demonstrate that N17350 selectively kills cancer cells, produces complete responses in mice, induces favorable innate/adaptive immunology, and identify histone H1 as a putative biomarker for efficacy. Thus, further studies in a clinical setting are warranted."

IO biomarker • Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • CD8 • ELANE • FAS

Onchilles Pharma Presents at SITC 2023 New Preclinical Data for N17350, a Potential Pan-Cancer Therapeutic (Businesswire) - "Onchilles Pharma...announced the presentation of new preclinical data for N17350 at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting....New data presented at SITC 2023 includes evidence of N17350’s ability to regress tumor growth in a human xenograft model of patient-derived ovarian cancer cell lines as well as colon, lung, and prostate cancers.....The results showed that histone H1 levels were elevated in cancer cells and correlated with N17350’s efficacy. Additional data demonstrate that N17350 selectively kills a wide range of cancer cells including those isolated from donor tissue of ovarian cancer patients."

Preclinical • Colon Cancer • Lung Cancer • Ovarian Cancer • Prostate Cancer

Onchilles Pharma Announces Presentation of Data for N17350 Program at SITC 2023 (Businesswire) - "Onchilles Pharma...announced today the presentation of preclinical data for the N17350 program at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting, to be held virtually and at the San Diego Convention Center from November 1-5, 2023....The company is targeting to start first-in-human clinical trials in skin cancers, head and neck cancer, and triple-negative breast cancer in 2024."

New trial • Preclinical • Breast Cancer • Head and Neck Cancer • Oncology • Skin Cancer • Solid Tumor • Triple Negative Breast Cancer

N17350 is an emerging therapeutic modality that selectively kills cancer cells and stimulates anti-tumor immunity (AACR 2023) - "Effects on primary and metastatic tumor growth, immunology, and survival were assessed in comparison to SoC agents (oxaliplatin, cyclophosphamide) or in combination with a checkpoint inhibitor (anti-CTLA4). N17350 killed and induced ICD markers in all cancer cell types tested without harming non-cancer cells, while SoC agents were similarly toxic to both cell types. Taken together, our data suggest that N17350 selectively kills cancer cells, produces complete responses in a subset of mice, induces favorable innate and adaptive immunology, and combines with checkpoint inhibitors in cold and hot tumors. Its ability to escape resistance, produce abscopal effects, and outperform SoC chemotherapies warrants further studies of this unique therapeutic modality in a clinical setting."

IO biomarker • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • CD8 • ELANE • FAS

Onchilles Pharma Presents at AACR 2023 New Preclinical Data on N17350, a First-in-Class Immuno-Oncology Drug Candidate with Broad, Potent, and Direct Tumor Killing Activity (Businesswire) - "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...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."

New P1 trial • Preclinical • Breast Cancer • Head and Neck Cancer • Melanoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Triple Negative Breast Cancer

Onchilles Pharma Announces Presentation of Preclinical Data for N17350 at AACR 2023 (Businesswire) - "Onchilles Pharma...announced today the presentation of preclinical data for N17350 at the American Association for Cancer Research (AACR) Annual Meeting 2023, to be held April 14 to 19 at the Orange County Convention Center in Orlando, Florida. Onchilles’ lead drug development candidate, N17350, is a first-in-class biologic therapeutic that is inspired by the immunobiology of neutrophils, a key part of the innate immune system, with the potential to be effective against a wide range of cancer types. The company is targeting to start first-in-human clinical trials in 2024."

New P1 trial • Preclinical • Oncology • Solid Tumor

Onchilles Pharma Nominates First Drug Development Candidate Leveraging Neutrophil Biology for the Treatment of Cancer (Businesswire) - "Alain P. Algazi...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.'"

Media quote

Onchilles Pharma Nominates First Drug Development Candidate Leveraging Neutrophil Biology for the Treatment of Cancer (Businesswire) - "Onchilles Pharma...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....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 checkpoint inhibitors in tumor models non-responsive to checkpoint blockade."

New trial • Preclinical • Oncology • Solid Tumor