Codiak Presents Preclinical Data at SITC 2020 Demonstrating Potential of engEx™ Engineered Exosomes to Stimulate Targeted, Integrated Anti-Tumor Immunity

– exoIL-12™ demonstrates tissue-retained pharmacology, enhanced anti-tumor activity, potent M1 myeloid recruitment, and superior T cell responses in vivo –

– Engineered exosomes with directed cellular tropism achieve targeted payload delivery –

CAMBRIDGE, Mass., Nov. 09, 2020 (GLOBE NEWSWIRE) — Codiak BioSciences, Inc. (NASDAQ: CDAK), a clinical-stage company focused on pioneering the development of exosome-based therapeutics as a new class of medicines, today announced that preclinical data from programs using its engEx™ Platform are being presented this week at the 35^th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). Results from multiple studies highlight the potential of Codiak’s precision engineered exosomes to direct pharmacological payloads to specific cells and to achieve enhanced immune mediated anti-tumor activity with an expanded safety margin.

Exosomes are naturally occurring, extracellular vesicles that have evolved as an intercellular messenger system to protect and deliver functional macromolecules between cells. Utilizing its engEx Platform, Codiak can engineer exosomes with distinct properties, load them with various types of therapeutic molecules and alter tropism so they reach specific cellular targets. Codiak is developing exosome therapeutic candidates to target multiple pathways throughout the body to treat various forms of cancer, neurological diseases, and infectious diseases. The company initiated clinical trials in September 2020 for two engineered exosome candidates, exoIL-12 and exoSTING™, for the treatment of lymphoid and solid tumors.

“These data provide further in vivo evidence that we can effectively harness the inherent biology of exosomes to improve the therapeutic window for selectively delivering potent drug molecules to engage promising targets that have eluded other approaches,” said Douglas E. Williams, Ph.D., President and Chief Executive Officer of Codiak. “With both of our lead oncology clinical programs now underway, we look forward to seeing results from the healthy volunteer portion of our exoIL-12 study by the end of the year and safety, biomarker and preliminary efficacy data from both exoIL-12 and exoSTING programs by the middle of next year.”

Tumor-Retained Pharmacology and Superior In Vivo Efficacy of exoIL-12 Widens the Therapeutic Window
exoIL-12 is a novel exosome therapeutic candidate engineered to display active IL-12 on the surface of the exosome. exoIL-12 facilitates potent local pharmacology at the injection site with precisely quantified doses with minimal systemic exposure. The current studies extend observations from previous presentations demonstrating tumor retention and increased tumor growth inhibition across multiple mouse models. Additionally, these data demonstrate significant remodeling of the tumor microenvironment and confirm tissue-retained pharmacology in non-human primate models, thereby widening the therapeutic window for this potent cytokine. Highlights from the data presented at SITC 2020 include:

• exoIL-12 showed 15-fold improved retention at the injection site and demonstrated four-fold prolonged and improved interferon gamma (IFNγ) production as compared to recombinant IL-12 (rIL-12).
• exoIL-12 was ~100 fold more potent in tumor growth inhibition than rIL-12. Complete responses were observed in 63% of mice treated with exoIL-12 compared to 0% in mice treated with an equivalent dose of rIL-12.
• exoIL-12 showed dramatic change in the tumor microenvironment as evidenced by ~8-fold increase in cytotoxic T-cell infiltration and ~150-fold increase in M1 macrophage recruitment.
• In the non-human primates, exoIL-12 demonstrated tissue-localized pharmacology, local induction of IFNg, and lack of systemic exposure.

Engineered Exosomes Allow for Targeting of Multiple Immune Cell Types
Results from multiple in vitro and in vivo studies demonstrated the ability of the engEx Platform to alter cellular tropism and increase functional payload delivery in multiple immune cell types.

• Exosomes engineered to display several types of targeting domains on the surface exhibited greater association with the target cell types, including dendritic cells (DCs), T cells and B cells, both in vitro and in vivo.
• Notably, exosomes engineered to display scFabs targeting Clec9A resulted in increased uptake in Clec9A positive DCs that are important in generating anti-tumor immune responses.
• Anti-Clec9A exosomes loaded with a STING agonist induced pro-inflammatory cytokines in primary mouse DCs at levels up to 15-fold greater than an untargeted control exosome.
• Preliminary in vivo data show that intra-tumorally administered anti-Clec9A exosomes reduced the required STING agonist dose by 10-fold to control tumor growth and induced greater immune responses against tumor-associated antigens when compared to untargeted controls.

Data from the posters titled Exosome surface display of IL-12 results in tumor-retained pharmacology with superior potency and limited systemic exposure in non-human primates (709) and Engineered exosomes with altered cellular tropism achieve targeted STING agonist delivery and single-agent tumor control in vivo (703) will be presented on Wednesday, November 11 from 5:15-5:45 p.m. EST and on Friday, November 13 from 4:40-5:10 p.m. EST. The posters will be made available on the Publications & Presentations page of the Codiak website.

About exoIL-12™
exoIL-12 is Codiak’s exosome therapeutic candidate engineered to display 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. A Phase 1 clinical trial is currently underway with preliminary results from healthy volunteers anticipated by the end of 2020 and safety, biomarker, and preliminary efficacy results from CTCL patients anticipated in mid-2021.

About exoSTING™
exoSTING is Codiak’s exosome therapeutic candidate engineered to incorporate a proprietary STING (stimulator of interferon genes) agonist inside the lumen of the exosome while expressing the exosomal protein, PTGFRN, on the exosome surface to facilitate specific uptake in tumor-resident antigen presenting cells (APCs). Codiak believes that exoSTING has the potential to overcome certain limitations of free STING agonists and enhance the therapeutic index and selectivity of delivery to desired cells in the tumor microenvironment.

Codiak is developing exoSTING for the treatment of multiple solid tumors enriched in the target APCs. exoSTING has demonstrated encouraging activity in preclinical models and is now being evaluated in a Phase 1/2 clinical trial in patients with advanced/metastatic, recurrent, and injectable solid tumors. Safety, biomarker, and preliminary efficacy data from the dose-escalation phase of the trial is expected in mid-2021. Future development of exoSTING may be expanded to neuro-oncology indications such as glioblastoma and leptomeningeal cancer disease.

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 disease areas, spanning oncology, neuro-oncology, neurology, neuromuscular disease, and infectious disease.

Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, among other things, statements concerning the development and therapeutic potential of exoSTING and exoIL-12, including timing of release of data, and capabilities of Codiak’s engEx Platform. Any forward-looking statements in this press release are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. For a discussion of these risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in the final prospectus related to Codiak’s initial public offering filed with the Securities and Exchange Commission pursuant to Rule 424(b) of the Securities Act of 1933, as amended, as well as discussions of potential risks, uncertainties and other important factors in Codiak’s subsequent filings with the Securities and Exchange Commission. All information in this press release is current as of the date of this report, and Codiak undertakes no duty to update this information unless required by law. 

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