Onchilles Pharma Presents at AACR 2024 New Preclinical Data for N17350 and N17465 Demonstrating the Potential for Potent and Tumor-Selective Treatment

• 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

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 www.onchillespharma.com.

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