exoSTING / Codiak - LARVOL DELTA

Designing a Plug-and-Play System to Produce Engineered Extracellular Vesicles (ASGCT 2025) - "This concept was explored in the development of therapeutics such as exoSTING™, exoASO-STAT6™ and exoIL-12™, which have completed Phase 1 clinical studies within oncology applications. These technologies will be made available to the wider scientific community under a research license, or via Lonza's CDMO service offerings. Disease Focus of Abstract:None"

STAT6

A First-in-Human Study of CDK-002 (exoSTING) in Subjects With Advanced/Metastatic, Recurrent, Injectable Solid Tumors (clinicaltrials.gov) - P1/2 | N=27 | Completed | Sponsor: Codiak BioSciences | Active, not recruiting ➔ Completed

Metastases • Trial completion • Breast Cancer • Endocrine Cancer • Head and Neck Cancer • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • PD-L1

A First-in-Human Study of CDK-002 (exoSTING) in Subjects With Advanced/Metastatic, Recurrent, Injectable Solid Tumors (clinicaltrials.gov) - P1/2 | N=27 | Active, not recruiting | Sponsor: Codiak BioSciences | Recruiting ➔ Active, not recruiting | N=180 ➔ 27 | Trial primary completion date: Dec 2022 ➔ Aug 2022

Enrollment change • Enrollment closed • Trial primary completion date • Breast Cancer • Endocrine Cancer • Head and Neck Cancer • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • PD-L1

Codiak BioSciences Reports Second Quarter 2022 Financial Results and Operational Progress (GlobeNewswire) - "Anticipated Milestones and Events: (i) Initiate Phase 2 study of exoIL-12 in an expanded group of tumor types in 1H 2023; continue to monitor patients enrolled in Phase 1 study; (ii) Initiate Phase 2 study of exoSTING in bladder cancer in 1H 2023; continue to monitor patients enrolled in ongoing Phase 1/2 study, reporting additional data at an upcoming scientific conference."

New P2 trial • P1/2 data • Trial status • Bladder Cancer • Cutaneous T-cell Lymphoma • Genito-urinary Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma • Urothelial Cancer

Codiak Provides Platform-Validating Clinical Update and Data from Phase 1 Trials of exoSTING and exoIL-12 (GlobeNewswire) - P1/2 | N=180 | NCT04592484 | Sponsor: Codiak BioSciences | Plasma pharmacokinetic (PK) measurements of patients that received exoSTING showed no systemic exposure to the agonist. Further, analyses of available plasma biomarkers indicated a lack of systemic inflammatory cytokines detectable in blood after exoSTING administration....Within all dose cohorts, exoSTING was well-tolerated and no dose limiting toxicities or treatment-emergent adverse events of Grade 3 or higher were observed....Blood biomarker assessments conducted post dosing demonstrated dose-dependent activation of the STING pathway at doses 100-fold lower in comparison to other free STING agonists....Codiak has identified 12.0 mcg as the intended dose for intratumoral administration and plans to file a protocol amendment with FDA later this year to enable initiation of a Phase 2 trial of exoSTING in patients with bladder cancer (Muscle Invasive Bladder Cancer or MIBC) during the first quarter of 2023."

Biomarker • Clinical protocol • FDA event • New P2 trial • P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Codiak BioSciences Reports First Quarter 2022 Financial Results and Operational Progress (GlobeNewswire) - "First patients dosed in exoASO-STAT6 Phase 1 clinical trial in hepatocellular carcinomas anticipated during 1H 2022; Safety, PK, PD, objective response rate (ORR), and efficacy data in injected and non-injected tumors from dose escalation cohorts 1-5 in the Phase 1/2 trial of exoSTING and recommended Phase 2 dose expected in late 1H 2022; Initial safety, PK/PD and efficacy data from at least the first cohort of CTCL patients in the Phase 1 clinical trial of exoIL-12 anticipated in late 1H 2022."

Enrollment status • P1/2 data • Cutaneous T-cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Oncology • Solid Tumor

A First-in-Human Study of CDK-002 (exoSTING) in Subjects With Advanced/Metastatic, Recurrent, Injectable Solid Tumors (clinicaltrials.gov) - P1/2; N=180; Recruiting; Sponsor: Codiak BioSciences; Trial primary completion date: Nov 2021 ➔ Dec 2022

Clinical • Trial primary completion date • Breast Cancer • Endocrine Cancer • Head and Neck Cancer • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • MRI • PD-L1

Combination therapy of exoSTING, exoIL-12 activates systemic anti-tumor immunity (SITC 2021) - "Subsequent imaging and histology studies demonstrated enhanced T cell infiltration in the non-injected subcutaneous tumor with the combination therapy. Conclusions By combining both exosome immunotherapies with a checkpoint blockade, we are able to elicit systemic anti-tumor immune immunity in both injected and non-injected tumors."

Combination therapy • Melanoma • Oncology • Solid Tumor • IL12A

exoSTING demonstrates potent anti-tumor activity in a mouse model of leptomeningeal disease (SITC 2021) - "Conclusions exoSTING, which previously showed strong efficacy against primary melanoma in mouse models, has been demonstrated in this study to also suppress tumor growth and improve survival in the LMD context. Our study supports the therapeutic rationale for using exoSTING for the treatment of LMD."

Preclinical • Melanoma • Oncology • Solid Tumor • STING

Codiak Reports Positive Initial Data for exoSTING Phase 1/2 Trial Indicating Tolerability, Immune Activation, and Evidence of Tumor Shrinkage in Injected and Non-Injected Tumors in the First Three Dose Escalation Cohorts (GlobeNewswire) - P1/2, N=180; NCT04592484; Sponsor: Codiak BioSciences; "Codiak BioSciences, Inc...announced positive initial data for exoSTING, a novel engineered exosome therapeutic candidate currently being investigated in a Phase 1/2 clinical trial as a single agent for the treatment of multiple solid tumors...Plasma pharmacokinetic (PK) measurements of subjects that received exoSTING showed no systemic exposure to the agonist...Within the first three dose cohorts, exoSTING was generally well tolerated and no treatment-related adverse events were observed through the 28-day follow-up period and beyond....Data from all five cohorts including objective response data are expected in the first half of 2022..."

P1/2 data • Oncology • Solid Tumor

New Preclinical Data at SITC 2021 Show Broad Potential Utility of Codiak’s Engineered Exosomes (GlobeNewswire) - "exoSTING Demonstrates Potent Anti-Tumor Activity in a Mouse Model of Leptomeningeal Disease...In a mouse model of leptomeningeal disease (LMD), an aggressive cancer of the central nervous system that occurs when primary tumors, typically from lung, breast and melanoma cancers, spread to the intracranial space, exoSTING improved overall survival in a dose-dependent manner with 100% complete response rates observed in the three highest doses tested. Further analyses showed localized anti-tumor immune response associated with exoSTING, including infiltration of tumor-specific T cells and macrophages and evidence of immunological memory without systemic inflammation."

Preclinical • Oncology

New Preclinical Data at SITC 2021 Show Broad Potential Utility of Codiak’s Engineered Exosomes (GlobeNewswire) - "Combination Therapy of exoSTING and exoIL-12 Activates Systemic Anti-Tumor Immunity...Specifically, the combination provided 93% and 78% tumor growth inhibition (TGI) in injected and non-injected tumors, respectively, in an anti-PD-1 refractory melanoma tumor model, compared to 44% TGI in non-injected tumors with exoSTING and 48% with exoIL-12 alone. This abscopal effect was also observed in multiple subcutaneous colorectal tumor and melanoma models when exoSTING and exoIL-12 were added to an anti-PD-1 checkpoint inhibitor. This triple combination resulted in up to 100% complete responses in both injected and non-injected tumors and, upon rechallenge, no new tumors grew, demonstrating lasting immunological memory. Subsequent analyses revealed enhanced T cell infiltration in the non-injected tumors associated with the combination therapy, suggesting that exosome-based immunotherapy can elicit an immune response that is both tumor-specific and systemic."

Preclinical • Oncology

Codiak BioSciences Reports Third Quarter 2021 Financial Results and Recent Operational Progress (GlobeNewswire) - "Three poster presentations at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2021) on November 12 and 13, including new preclinical data on exoASO-STAT6 in hepatocellular carcinoma...and the combination of exoSTING and exoIL-12 in solid tumors. Initial safety, PK, and PD data from dose escalation cohorts 1-3 on the Phase 1/2 trial of exoSTING in patients with advanced/metastatic solid tumors with injectable lesions expected in the fourth quarter of 2021. IND filing for exoASO-STAT6 anticipated during the fourth quarter of 2021. Initial safety, PK/PD and efficacy data in CTCL patients are now expected in the first half of next year due predominantly to COVID-related restrictions in the U.K. that are impacting the Phase 1 clinical trial sites for exoIL-12."

IND • Preclinical • Cutaneous T-cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Oncology • Solid Tumor

Codiak BioSciences Reports Second Quarter 2021 Financial Results and Operational Progress (GlobeNewswire) - “Initial safety, PK, and PD data from dose escalation cohorts 1-3 on the Phase 1/2 trial of exoSTING (CDK-002) in patients with advanced/metastatic solid tumors with injectable lesions expected in the fourth quarter of 2021…Research and development expenses were $15.4 million for the quarter ended June 30, 2021, compared to $11.6 million for the same period in 2020. The increase in research and development expenses was driven by an increase in engEx Platform expenses, partially offset by decreased manufacturing and preclinical costs as Codiak’s lead candidates progressed into the clinic during the second half of 2020.”

Commercial • P1/2 data • Oncology • Solid Tumor

ExoSTING, an extracellular vesicle loaded with STING agonists, promotes tumor immune surveillance. (PubMed, Commun Biol) - "ExoSTING at therapeutically active doses did not induce systemic inflammatory cytokines, resulting in an enhanced therapeutic window. ExoSTING is a novel, differentiated therapeutic candidate that leverages the natural biology of EVs to enhance the activity of CDNs."

Journal • Immunology • Inflammation • Oncology • CD8 • STING

Data from Codiak’s exoSTING Preclinical Development Program for the Treatment of Solid Tumors Published in the Nature Research Publication, Communications Biology (GlobeNewswire) - “…exoSTING demonstrates greater than 100-fold increased potency in in vivo tumor models and increased tumor retention and lower levels of systemic inflammatory cytokine production as compared to free STING agonist (delivered without exosomes). Additionally, exoSTING demonstrates CD8 T-cell preservation, expansion, Th1 polarization and establishment of systemic antigen-specific T-cell mediated immune responses across a wide dose range without evidence of immune ablation as seen with free STING agonists. A Phase 1/2 dose escalation clinical trial of exoSTING is currently underway…Safety, biomarker and preliminary efficacy data from the dose-escalation phase of the trial are expected in mid-2021.”

P1/2 data • Preclinical • Oncology • Solid Tumor

Codiak BioSciences Reports Fourth Quarter and Full Year 2020 Financial Results and Operational Progress (GlobeNewswire) - “Research and development expenses were $74.0 million for the year ended December 31, 2020 compared to $59.5 million for the same period in 2019. The year-over-year increase was primarily driven by an increase in license milestones, personnel costs, and clinical development expenses related to the initiation of the exoIL-12 and exoSTING clinical trials in September 2020.”

Commercial • Oncology

Codiak BioSciences Reports Fourth Quarter and Full Year 2020 Financial Results and Operational Progress (GlobeNewswire) - "Late-breaking abstract poster presentation of the full Pharmacokinetic/pharmacodynamic and tolerability data from healthy volunteer portion of the exoIL-12 Phase 1 clinical trial at the American Association for Cancer Research (AACR) Annual Meeting, to be held April 10-15, 2021; Poster presentation of preclinical data from the exoASO-STAT6 program at the AACR Annual Meeting, to be held April 10-15, 2021; Safety and preliminary pharmacodynamics and efficacy data from exoSTING Phase 1/2 clinical trial in patients with solid tumors expected mid-2021; Investigational New Drug (IND) application filing for exoASO-STAT6 program to enable initiation of clinical trials anticipated during the second half of 2021; Biomarker, safety and preliminary pharmacodynamics and efficacy data in CTCL patients from exoIL-12 Phase 1 trial expected by year-end 2021."

IND • P1 data • P1/2 data • Preclinical • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma

A First-in-Human Study of CDK-002 (exoSTING) in Subjects With Advanced/Metastatic, Recurrent, Injectable Solid Tumors (clinicaltrials.gov) - P1/2; N=180; Recruiting; Sponsor: Codiak BioSciences

Clinical • New P1/2 trial • Anaplastic Thyroid Cancer • Breast Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Thyroid Cancer • Triple Negative Breast Cancer • PD-L1

Phase update (Businesswire) - Preclinical➔P2, Oncology

Phase shift • Oncology

Codiak Initiates Patient Dosing in Phase 1/2 Clinical Trial of exoSTING for the Treatment of Solid Tumors (Businesswire) - “Codiak BioSciences, Inc…announced the initiation of patient dosing in its Phase 1/2 clinical trial of exoSTING…The trial, which will study exoSTING in solid tumors, is Codiak’s second human clinical trial and the second clinical development program the Company has initiated in the past month….Safety, biomarker and preliminary efficacy data from the dose-escalation phase of the trial is expected in mid-2021. As part of the Phase 2 portion of the trial, Codiak intends to enroll further expansion cohorts of patients at the optimal exoSTING dose to be identified in the Phase 1 portion of the clinical program.”

P1/2 data • Trial status • Oncology • Solid Tumor

Codiak presents new preclinical data for first-in-class exosome therapeutic candidates, exoIL-12 and exoSTING, demonstrating potent anti-tumor activity (Businesswire) - "Codiak BioSciences, Inc...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....'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.'"

New trial • Preclinical

Selective activation of antigen presenting cells by exoSTING enhances tumor antigen-specific immune response (SITC 2019) - "ExoSTING(tm) is an engineered exosome therapeutic candidate that specifically targets the STING pathway in APCs in the tumor microenvironment, resulting in enhanced PD effects, avoidance of T cell uptake and enhanced anti-tumor immune responses compared to free CDN. Human clinical testing is planned to begin in the first half of 2020."

IO Biomarker • PD(L)-1 Biomarker