CAMBRIDGE, Mass.--(BUSINESS WIRE)--Codiak BioSciences, Inc., 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.
About the engEx™ Platform
Codiak’s proprietary engEx Platform is designed to enable the development of engineered exosome therapeutics for a wide spectrum of diseases and to manufacture them reproducibly and at scale to pharmaceutical standards. By leveraging the inherent biology, function and tolerability profile of exosomes, Codiak is developing engEx exosomes designed to carry and protect potent drug molecules, provide selective delivery and elicit the desired pharmacology at the desired tissue and cellular sites. Through its engEx Platform, Codiak seeks to direct tropism and distribution by engineering exosomes to carry on their surface specific targeting drug moieties, such as proteins, antibodies/fragments, and peptides, individually or in combination. Codiak scientists have identified two exosomal proteins that serve as surface and luminal scaffolds. By engineering the exosome surface or lumen and optimizing the route of administration, Codiak aims to deliver engEx exosomes to the desired cell and tissue to more selectively engage the drug target, potentially enhancing the therapeutic index by improving potency and reducing toxicity.
About Codiak BioSciences
Codiak is a clinical-stage biopharmaceutical company focused on pioneering the development of exosome-based therapeutics, a new class of medicines with the potential to transform the treatment of a wide spectrum of diseases with high unmet medical need. By leveraging the biology of exosomes as natural intercellular transfer mechanisms, Codiak has developed its proprietary engEx Platform to expand upon the innate properties of exosomes to design, engineer and manufacture novel exosome therapeutic candidates. Codiak has utilized its engEx Platform to generate a deep pipeline of engineered exosomes aimed at treating a broad range of diseases, spanning oncology, neuro-oncology, neurology, neuromuscular disease and infectious disease. For more information, visit http://www.codiakbio.com.