Codiak BioSciences, a clinical-stage company focused on pioneering the development of exosome-based therapeutics as a new class of medicines, today announced the initiation of subject dosing in its Phase 1 clinical trial of its novel exosome therapeutic candidate, exoIL-12. Engineered using Codiak’s proprietary engEx Platform and designed to display IL-12 on the exosome surface, exoIL-12 is designed to enhance dose control of IL-12 and limit systemic exposure and associated toxicity by localizing IL-12 in the tumor microenvironment (TME). The trial will evaluate single ascending doses (SAD) of exoIL-12 in healthy volunteers and then transition to patients with early stage cutaneous T cell lymphoma (CTCL) with repeat dosing of pharmacologically active doses identified in the healthy volunteer SAD study. The trial is Codiak’s first human clinical trial and the first of two clinical development programs Codiak expects to initiate in 2020.
“To our knowledge, exoIL-12 is the first engineered exosome to enter clinical development, which makes the initiation of this trial a true milestone not only for Codiak but for the entire exosome therapeutics field,” said Douglas E. Williams, Ph.D., CEO, Codiak. “Our engEx platform allows us to engineer exosomes to selectively deliver potent therapeutic payloads, such as IL-12, to potentially enhance the therapeutic index. We believe that exoIL-12 may unlock the well-documented therapeutic potential of this cytokine by retaining its activity within the tumor and reducing systemic exposure and the adverse events seen in the past with other formulations of IL-12.”
Codiak is initially focusing development of exoIL-12 on tumors that have previously shown clinical responses to IL-12 used as a monotherapy, such as CTCL. While the biological rationale for IL-12 as a cancer treatment has been validated in previous human clinical studies, its utility has been severely limited due to serious adverse events caused by systemic exposure.
Codiak has engineered exoIL-12 to display fully active IL-12 on the surface of the exosome, which is designed to facilitate potent local pharmacology at the tumor injection site with precisely quantified doses. Exosomal delivery has demonstrated limited systemic exposure to IL-12 in preclinical models and resulted in significant and prolonged pharmacodynamic activity and both local and systemic anti-tumor immune responses.
The Phase 1 clinical trial, which is being conducted at the Phase 1 unit Richmond Pharmacology LTD, London, UK, is designed to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of exoIL-12 following single ascending subcutaneous doses in healthy volunteers, followed by repeat dose exoIL-12 into the lesions of stage IA-IIB CTCL patients. Patients with CTCL will be monitored for safety, pharmacokinetics, pharmacodynamic effects in blood and tumor biopsies, and local and systemic anti-tumor efficacy using validated CTCL assessment criteria. Preliminary results from healthy volunteers are anticipated by the end of 2020 and safety, biomarker and preliminary efficacy results from CTCL patients are anticipated in mid-2021.
exoIL-12 is Codiak’s exosome therapeutic candidate engineered to display fully active IL-12 on the surface of the exosome, using the exosomal protein, PTGFRN, as a scaffold protein, and designed to facilitate potent local pharmacology at the injection site with precisely quantified doses. By limiting systemic exposure of IL-12 and associated toxicity, Codiak hopes to enhance the therapeutic index with exoIL-12, delivering a more robust tumor response, dose control and an improved safety profile.
Codiak intends to focus development of exoIL-12 on tumors that have, in previous clinical testing, shown clinical responses to IL-12 used as a monotherapy. This includes cutaneous T cell lymphoma (CTCL), melanoma, Merkel cell carcinoma, Kaposi sarcoma, glioblastoma multiforme and triple negative breast cancer.
Source – BusinessWire