Codiak Presents New Preclinical Data for First-in-Class Exosome Therapeutic Candidates, exoIL-12 and exoSTING, Demonstrating Potent Anti-Tumor Activity
- Category: Proteins and Peptides
- Published on Saturday, 09 November 2019 10:15
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– exoIL-12 demonstrates tumor-retained and dose-dependent pharmacology with superior anti-tumor efficacy compared to soluble recombinant IL-12 –
– exoSTING shows unique pharmacodynamic effects and tumor antigen-specific systemic immune responses compared to free STING agonist –
– Company plans to initiate clinical trials for exoIL-12 and exoSTING in 2020 –
CAMBRIDGE, MA, USA I November 08, 2019 I Codiak BioSciences, Inc., a company pioneering exosomes as a new class of biologic medicines, today announced new preclinical data for its lead engEx™ Platform therapeutic candidates, exoIL-12™ and exoSTING™. Results from multiple studies highlight the potential of Codiak’s precision engineered exosomes to direct pharmacological payloads to specific cells and achieve superior anti-tumor efficacy compared to conventional therapeutic approaches. These data are being presented this week at the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in National Harbor, MD.
“We believe our engEx Platform can fulfill the promise of exosomes, overcoming significant hurdles that have faced the therapeutic development of many promising pathways in the past. We are particularly excited to debut data for exoIL-12 that show how engineered exosomes can direct biological activity to the tumor, re-opening the door for drug development for this long attractive target,” said Douglas E. Williams, Ph.D., President and Chief Executive Officer of Codiak. “We are focused on advancing our initial candidates, exoSTING and exoIL-12, through IND-enabling preclinical studies and plan to initiate proof-of-concept clinical trials for both programs in 2020.”
Both exoIL-12 and exoSTING were developed via Codiak’s proprietary engEx Platform, which enables the company to design exosomes – nature’s intercellular messengers – with precisely engineered properties, to incorporate various types of biologically active molecules and to be directed to specific cell types and tissues.
exoIL-12 is a precision engineered exosome therapeutic candidate expressing active IL-12 on the surface of the exosome via Codiak’s novel protein scaffold, PTGFRN. The data from exoIL-12 in vivo preclinical studies highlight the unique potential of engEx exosomes to direct and retain IL-12 pharmacology at the tumor injection site, driving significantly greater anti-tumor activity than soluble recombinant IL-12 (rIL-12) and inducing antigen-specific systemic immunity.
- Following intratumoral (IT) injection, exoIL-12 was ~100-fold more potent in tumor growth inhibition than rIL-12.
- 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 rIL-12.
- exoIL-12 stimulated a dose-dependent reduction in tumor growth in primary IT injected and distal tumors.
- Complete responses were observed in ~2/3 of mice treated with exoIL-12 compared to 0% in mice treated with an equivalent dose of rIL-12.
- Re-challenge studies of complete responders from the exoIL-12 group showed no tumor regrowth, demonstrating immunologic memory T-cell activity.
Data from the poster titled Exosome surface display of IL-12 results in tumor-retained pharmacology with superior potency and limited systemic exposure compared to recombinant IL-12 (P785) will be presented on Friday, November 8th.
exoSTING is a precision engineered exosome therapeutic candidate overexpressing the protein PTGFRN, which promotes uptake selectively into antigen presenting cells (APCs) and is loaded with a proprietary synthetic cyclic dinucleotide to stimulate the STING (stimulator of interferon genes) pathway. Consistent with Codiak’s previously reported data, these preclinical studies emphasize exoSTING’s selective activation of the STING pathway in tumor-resident APCs, lack of immune cell ablation in the tumor, generation of antigen-specific T-cell responses and establishment of immunological memory. In addition, preliminary ex vivo studies with human tumor samples confirm the unique biology of exoSTING.
- In vitro, exoSTING demonstrated a 100-fold increase in potency of macrophage activation compared to a free STING agonist, as well as selective activation of M2 immunosuppressive macrophages that drive immune responses against tumors.
- In vivo in a checkpoint refractory abscopal tumor model, exoSTING preserved the viability of T-cells and APCs, reduced nonspecific tissue damage and recruited T-cells into tumors, whereas free STING agonist resulted in immune cell ablation.
- exoSTING increased T-cell infiltration in the tumor microenvironment by four-fold compared to free STING agonist.
- exoSTING inhibited tumor growth in both injected and non-injected contralateral tumors, suggesting systemic anti-tumor response.
- exoSTING preserved immunological memory response as demonstrated by tumor re-challenge studies. Complete responders showed no tumor regrowth.
- Initial ex vivo analyses demonstrated that exoSTING activates the STING pathway in human tumor tissues after IT administration.
Data from the poster titled Selective activation of antigen presenting cells by exoSTING enhances tumor antigen-specific immune response (P666) will be presented on Saturday, November 9th.
exoIL-12 is a precision engineered exosome therapeutic candidate expressing IL-12 on the surface of the exosome by molecular fusion to Codiak’s proprietary scaffold protein, PTGRFN. Developed via Codiak’s proprietary engEx™ Platform, exoIL-12 is designed to target T-cells and Natural Killer cells and induce systemic anti-tumor immunity. Data from Codiak’s preclinical studies suggest that when administered intratumorally, exoIL-12 is retained in the tumor microenvironment, thus resulting in potent anti-tumor immunity and an improved toxicity profile compared to recombinant IL-12. Codiak plans to begin its first Phase 1/2 clinical trial for exoIL-12 initially in patients with Cutaneous T-Cell Lymphoma in the second half of 2020.
exoSTING is a precision engineered exosome therapeutic candidate that is surface engineered with the protein PTGFRN, and luminally loaded with a proprietary, potent small molecule STING (stimulator of interferon genes) agonist. Developed via Codiak’s proprietary engEx™ Platform, exoSTING is designed to selectively activate the STING pathway in tumor-resident antigen presenting cells (APCs) and attract and expand immune effector cells in the tumor microenvironment. Data from Codiak’s preclinical studies suggest that when administered intratumorally, exoSTING generates potent, targeted and sustained anti-tumor immunity in numerous preclinical models without systemic elevation of inflammatory cytokines. Codiak plans to initiate its first Phase 1/2 clinical trial for exoSTING in patients with a select group of solid tumors in the first half of 2020.
About Codiak BioSciences
Codiak BioSciences is harnessing exosomes—natural intercellular messengers—to pioneer a new class of biologic medicines, exosome therapeutics. Utilizing our proprietary and versatile exosome engineering and manufacturing platform (engEx™ Platform), Codiak is developing exosomes with precisely engineered properties to engage pathways and deliver potent therapeutics to specific cell targets. We are building a broad pipeline of therapeutic candidates that may have a transformative impact on the treatment of many diseases, including in the areas of oncology, immune-based diseases, fibrotic disorders, neurological disorders and rare diseases. For more information, visit http://www.codiakbio.com.
SOURCE: Codiak BioSciences