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Tumor-directed N17350 and systemically delivered N17465 are based on the breakthrough discovery of a novel innate immune mechanism of action, which activates cell death pathways specific to cancer cells New preclinical data demonstrate direct and tumor-selective efficacy of N17350 in both chemotherapy-naïve and -experienced ovarian cancer patient cells and cell-derived xenograft (CDX) models First data from the N17465 program demonstrate that the advanced drug lead can be delivered intravenously (IV) to induce potent single agent efficacy resulting from direct cancer cell killing and induction of anti-tumor immunity across a range of solid tumor models Onchilles is on-track to initiate first-in-human clinical trials this year to evaluate N17350 in skin cancers, head and neck cancer, and triple-negative breast cancer SAN DIEGO--(BUSINESS WIRE)-- Onchilles Pharma, a private biotech company developing cancer therapeutics that leverage a novel innate immune mechanism of action for potent and selective cancer killing, announced today the presentation of new preclinical data for systemically delivered N17465 in an oral presentation and tumor-directed N17350 in a poster presentation at the American Association for Cancer Research® (AACR) Annual Meeting 2024, taking place April 5 to 10 at the San Diego Convention Center. N17350 and N17465 are novel first-in-class oncology programs that harness the potent efficacy of the innate immune system and have the potential to become a major new treatment modality for a wide range of cancer types. Onchilles has engineered N17350 for intratumoral delivery and N17465 for systemic IV delivery and generated significant preclinical data validating the novel mechanism of action that delivers efficacy independent of tumor genetics and immune status by targeting the histone H1-death domain axis. Upregulation of histone H1 is a property common to many cancer cells and responsible for the selectivity of cancer cell killing seen in the N17350 and N17465 programs via immunogenic cell death. Lev Becker, Ph.D., Scientific Founder, Onchilles Pharma, said, “We are excited to unveil systemically delivered N17465 that has the potential to redefine the treatment of solid tumors. The data presented today demonstrate that N17465 exhibits potent and tumor-selective efficacy, mobilizes the immune system for anti-tumor immunity, and produces durable responses in mouse models as a monotherapy. These data mark a major step forward in our quest to bring N17465 to patients.” Dr. Becker continued, “The new data presented today for N17350 add to our large preclinical data package validating the mechanism of action, confirming it induces immunogenic tumor cell death, and demonstrating selective cancer-cell killing in patient-derived chemotherapy-naive or -experienced ovarian cancer cell lines and CDX models. We believe that these data underscore the potential of N17350 as a potent and safe cancer treatment, and we look forward to advancing tumor-directed N17350 into first-in-human clinical trials this year.” Court R. Turner J.D., Co-Founder & Executive Chair of Onchilles Pharma, said, “The latest data revealed at AACR on primary tumor samples introduce a significant layer of human validation to our approach before our planned clinical trials. The potent single-agent activity and selectivity of N17350 distinguish it from other tumor-directed approaches currently in development that only show modest to no monotherapy efficacy. We are confident that N17350 and N17465 represent a novel class of molecules that could become the new foundation of cancer treatment. We anticipate strong monotherapy efficacy of N17350 in our upcoming Phase 1 trial with potential approvals in many types of solid tumors by 2028, marking a significant milestone in oncology.” Details of the data presented are as follows: In a talk for abstract 6578, entitled, “N17465, a systemically deliverable elastase, attenuates tumorigenesis and stimulates anti-tumor immunity,” the following data were presented: N17465 resisted inhibition by serine protease inhibitors found in the blood and maintained its ability to cleave the death domain of CD95 (therapeutic target) to selectively kill cancer cells. N17465 induced immunogenic cell death (ICD) markers in cancer cell lines and patient ovarian cancer cells and was also well tolerated by non-cancer cells. Systemically delivered N17465 produced tumor-free mice in a murine CT26 colon cancer model and induced a favorable immune profile. N17465 also exhibited efficacy across a range of xenograft models spanning human lung, colon, breast, and prostate cancer, as well as ovarian cancer patient-derived CDX models. In a poster for abstract 5895 entitled, “N17350 kills cancer cells, spares immune cells, and regresses CDX tumors from chemotherapy-naive and experienced patients,” the following data were presented: 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 rapidly regressed tumors in all OvCa CDX models and exhibited markedly improved efficacy over carboplatin. N17350 mobilizes anti-tumor immunity in the 4T1 model of metastatic breast cancer and outperforms standard-of-care chemotherapy. About N17350 and N17465 and Their Novel Mechanism of Action 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 selectively and potently kills cancer cells independent of their genetics and anatomical origin, mobilizes adaptive immunity, and avoids resistance mechanisms. The team at Onchilles translated this ground-breaking discovery into a proprietary set of molecules, including N17350 and N17465, with the potential to treat a wide variety of tumor types with an optimal efficacy and safety profile. About Onchilles Pharma Onchilles Pharma is a global drug discovery and development company that leverages novel innate immuno-biology to develop the next generation of cancer therapies. These first-in-class therapeutics exploit a novel fundamental mechanism of action to treat cancer independent of its genetic background or anatomical origin. The company is developing a pipeline of first-in-class biologic drug candidates and plans to start first-in-human clinical trials for its first program, N17350, in 2024 in skin cancers, head and neck cancer, and triple-negative breast cancer. For more info, visit .

SAN DIEGO--(BUSINESS WIRE)-- Onchilles Pharma, a private biotech company developing cancer therapeutics that leverage a novel mechanism of action, announced the presentation of new preclinical data for N17350 at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting being held virtually and at the San Diego Convention Center from November 1-5, 2023. The data presented show the potential for N17350, a first-in-class biologic therapeutic inspired by the immunobiology of neutrophils, to become a major new treatment modality for a wide range of cancer types. “Our lead drug candidate, N17350, shows a unique combination of potent and selective cancer cell killing and immune activation with the potential to eradicate tumors irrespective of their genetic makeup and anatomical origin,” said Lev Becker, Ph.D., Scientific Founder and Board Member of Onchilles Pharma. “These new data presented at SITC reveal the efficacy of N17350 in difficult-to-treat human xenograft models and establishes a correlation between N17350’s efficacy and elevated histone H1 levels, which are upregulated in cancer cells.” 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. This builds upon previously presented data at AACR 2023 showing N17350 efficacy in syngeneic colon (CT26) and metastatic breast (4T1) cancer models. To understand histone H1’s role in this novel mechanism of action, Onchilles’ scientists compared histone H1 levels in cancer cells to non-cancer cells. 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. Taken together, these findings support a potential broad therapeutic window for this innovative cancer cell-killing mechanism. “The new preclinical data reported further highlights the broad clinical potential of our lead candidate, N17350, for a wide range of cancer types,” said Court R. Turner J.D., Co-Founder and Executive Chair of Onchilles Pharma. “We are on track with our preclinical development efforts which will support advancing N17350 to the clinic next year in skin cancers, head and neck cancer, and triple-negative breast cancer, where treatment options are extremely limited.” About N17350 and Its Novel Mechanism of Action 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 selectively and potently kills cancer cells independent of their genetics and anatomical origin, mobilizes adaptive immunity, and avoids resistance mechanisms. The team at Onchilles translated this ground-breaking discovery into a proprietary set of molecules, including N17350, with the potential to treat a wide variety of tumor types with an optimal efficacy and safety profile. About Onchilles Pharma Onchilles Pharma is a global drug discovery and development company that leverages novel innate immuno-biology to develop the next generation of pan-cancer therapies. These first-in-class therapeutics exploit a novel fundamental mechanism of action to treat cancer independent of its genetic background or anatomical origin. The company is developing a pipeline of first-in-class biologic drug candidates and plans to start first-in-human clinical trials for its first program, N17350, in 2024 in skin cancers, head and neck cancer and triple negative breast cancer. For more info, visit .

- 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 & ORLANDO, Fla.--(BUSINESS WIRE)-- 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,” said 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.” 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. For more info, visit .