exoASO-STAT6 / 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"

Oncology • STAT6

A Study of exoASO-STAT6 (CDK-004) in Patients With Advanced Hepatocellular Carcinoma (HCC) and Patients With Liver Metastases From EIther Primary Gastric Cancer or Colorectal Cancer (CRC) (clinicaltrials.gov) - P1 | N=9 | Terminated | Sponsor: Codiak BioSciences | N=30 ➔ 9 | Trial completion date: Apr 2024 ➔ May 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Oct 2023 ➔ May 2023; Company Bankruptcy

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

A Study of exoASO-STAT6 (CDK-004) in Patients With Advanced Hepatocellular Carcinoma (HCC) and Patients With Liver Metastases From EIther Primary Gastric Cancer or Colorectal Cancer (CRC) (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Codiak BioSciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Preclinical PK/PD profile, biomarker identification and rationale for indication selection of exoASO-STAT6™, a selective tumor-associated macrophage targeting candidate (SITC 2022) - "Analysis of The Cancer Genome Atlas database identified several tumor indications in which high expression of a macrophage-STAT6 signature correlates with poor survival, including HCC, stomach, and bladder cancer (p=0.012, p=0.00056, and p=0.0021, respectively). Conclusions In summary, we demonstrated that exoASO-STAT6 has a durable PK/PD profile in the liver of preclinical species, identified PD biomarkers with good clinical translational potential and described a rationale for selecting cancer subtypes that could benefit from treatment with exoASO-STAT6."

PK/PD data • Preclinical • Bladder Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Urothelial Cancer • IL4R • STAT6

Codiak Presents Preclinical Data on exoASO-STAT6 and exoASO-C/EBPβ Programs at the Society for Immunotherapy of Cancer (SITC) 2022 Annual Meeting (GlobeNewswire) - "Codiak BioSciences...announced new preclinical data from its exoASO™-STAT6 and exoASO™-C/EBPβ programs...Systemic administration of exoASO-STAT6 in mice and NHPs resulted in a durable, dose-dependent retention of the STAT6 ASO in the liver, detectable for up to 21 days at all dose levels."

Preclinical • Oncology • Solid Tumor

Codiak BioSciences Reports Third Quarter 2022 Financial Results and Operational Progress (GlobeNewswire) - "Continue enrollment in Phase 1 trial for exoASO-STAT6, with initial data expected in 1H 2023. Present new preclinical data for macrophage targeting programs exoASO-STAT6 and exoASO™-C/EBPβ at the Society for Immunotherapy of Cancer (SITC) in November 2022."

P1 data • Preclinical • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

Codiak to Present New Preclinical Data Demonstrating Potent Monotherapy Activity of Two Engineered Exosome Intravenous Candidates Targeting Macrophages (GlobeNewswire) - "Codiak BioSciences...announced that two posters featuring preclinical data from its engEx® Platform programs will be presented during the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2022)....'At SITC, we will present new preclinical data on two of our systemically administered exosome therapeutic candidates which target macrophages and have previously demonstrated potent monotherapy activity in preclinical models....Both exoASO™-STAT6 and exoASO™-C/EBPβ specifically inhibit transcription factors in distinct macrophage subpopulations by leveraging engineered exosomes to selectively target pathways known to play a critical role in tumor immunology'."

Preclinical • Oncology

Engineered exoASO-STAT6: a potent monotherapy for oral squamous cell carcinoma. (PubMed, Future Oncol) - No abstract available

Journal • Monotherapy • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • STAT6

Codiak Initiates Patient Dosing in Phase 1 Clinical Trial of exoASO-STAT6 in Patients with Advanced Hepatocellular Carcinoma, Liver Metastases from Primary Gastric Cancer and Colorectal Cancer (GlobeNewswire) - "Codiak BioSciences, Inc...announced the initiation of patient dosing in its Phase 1 clinical trial of exoASO-STAT6....The Phase 1 clinical trial will evaluate the safety, tolerability, biomarkers and preliminary anti-tumor activity of exoASO-STAT6 in patients with advanced hepatocellular carcinoma (HCC), patients with liver metastases from primary gastric cancer and colorectal cancer (CRC). The study is anticipated to enroll patients across four cohorts at sequentially escalating dose levels, with subjects in the initial cohorts receiving biweekly exoASO-STAT6 administered intravenously over the course of 28 days. Ultimately the trial may enroll up to 30 patients. Initial Phase 1 data are expected in the first half of 2023."

Trial status • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

A Study of exoASO-STAT6 (CDK-004) in Patients With Advanced Hepatocellular Carcinoma (HCC) and Patients With Liver Metastases From Primary Gastric Cancer and Colorectal Cancer (CRC) (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Codiak BioSciences

New P1 trial • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular 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

Exosome-mediated genetic reprogramming of tumor-associated macrophages by exoASO-STAT6 leads to potent monotherapy antitumor activity. (PubMed, Sci Adv) - "Administration of exoASO-STAT6 leads to induction of nitric oxide synthase 2 (NOS2), an M1 macrophage marker, resulting in remodeling of the tumor microenvironment and generation of a CD8 T cell-mediated adaptive immune response. Collectively, exoASO-STAT6 represents the first platform targeting transcription factors in TAMs in a highly selective manner."

IO biomarker • Journal • Monotherapy • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • CD8 • NOS2 • STAT6

Data from Codiak’s exoASO-STAT6 Preclinical Development Program for the Treatment of Primary and Metastatic Hepatic Cancers Published in Science Advances (GlobeNewswire) - "This publication details the findings from the preclinical development program and highlights the ability of exoASO-STAT6 to selectively target tumor associated immune-suppressive macrophages (TAMs) and precisely disrupt STAT6 signaling to generate impressive monotherapy anti-tumor activity in cancer models....Codiak plans to initiate in the first half of 2022 a Phase 1 clinical trial to evaluate the safety, tolerability, biomarkers and preliminary anti-tumor activity of exoASO-STAT6 in HCC."

New P1 trial • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

New Preclinical Data at SITC 2021 Show Broad Potential Utility of Codiak’s Engineered Exosomes (GlobeNewswire) - "When administered intravenously in preclinical models of HCC, exoASO-STAT6 demonstrated: Dose-dependent and durable oligonucleotide accumulation in liver models; Significant and durable STAT6 mRNA knockdown in murine and NHP models; Attenuation of tumor growth, including complete remission of tumor lesions in 50% of treated mice; Enhanced anti-tumor activity (75% complete remissions) when combined with anti-PD1 antibodies; and Consistent PK, PD and effective STAT6 silencing across in vitro and multiple in vivo settings."

Preclinical • Oncology

Codiak BioSciences Announces FDA Clearance of IND for exoASO-STAT6; Patient Dosing Expected 1H 2022 (GlobeNewswire) - "Codiak BioSciences, Inc...announced that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug Application (IND) for exoASO-STAT6....'We are eager to confirm this biological profile in the clinic and expect to begin enrolling patients in this Phase 1 study in the first half of 2022.'"

IND • New P1 trial • Colorectal Cancer • Glioma • Gynecologic Cancers • Hepatocellular Cancer • Lung Adenocarcinoma • Oncology • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma • Thyroid Gland Carcinoma • Uveal Melanoma

Exosome mediated reprogramming of tumor associated macrophages by exoASO-STAT6 for the treatment of Hepatocellular Carcinoma (HCC) (SITC 2021) - "Altogether our data support the systemic administration of exoASO-STAT6 as a promising therapy for liver cancer. For Mice Mice were maintained and treated at the animal care facility of Codiak Biosciences in accordance with the regulations and guidelines of the Institutional Animal Care and Use Committee (CB2017-001).Animal housing and experimental procedures (mice) were conducted according to the French and European Regulations and the National Research Council Guide for the Care and Use of Laboratory Animals and Institutional Animal Care and Use Committee of Oncodesign (Oncomet) approved by French authorities (CNREEA agreement N° 91).For cynomolgus monkeys:All animals were maintained and treated at the animal care facility of Altasciences in compliance with the Animal Welfare Act and recommendations set forth in the Guide for the Care and Use of Laboratory Animals (National Research Council 2011)."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • IL4R • STAT6

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 to Present Preclinical Data Demonstrating New Potential Therapeutic Applications of Engineered Exosomes at the Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - "Codiak BioSciences, Inc...announced that three posters featuring preclinical data from its engEx™ Platform programs will be presented during the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2021), which is being held virtually and in person in Washington, D.C. from November 10-14, 2021...'In addition, we will share new data in hepatocellular carcinoma models with our next clinical candidate, exoASO-STAT6, for which we expect to file an IND by the end of the year.'"

IND • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

[VIRTUAL] Engineered exosome- mediated STAT6 knockdown in tumor associated macrophages (TAMs) results in potent single agent activity in a hepatocellular carcinoma (HCC) model (AACR 2021) - "exoASO-STAT6 is a novel therapeutic that selectively targets STAT6, a key transcription factor in TAMs. This therapy results in effective macrophage reprogramming to a pro-inflammatory M1 phenotype and potent single agent anti-tumor activity in multiple checkpoint refractory tumor models. In sum, exoASO-STAT6 represents a first-in-class strategy to target TAMs in a highly selective manner."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD163 • CD8 • IL12A • IL1B • STAT6 • TGFB1 • TNFA

[VIRTUAL] Engineered Exosomes Efficiently Deliver STAT6 Antisense Oligonucleotides to Tumor Associated Macrophages (TAMs) Resulting in Potent Local and Systemic Anti-Tumor Activity (ASGCT 2021) - "A significant increase in interferon and cytotoxic T-cell gene signatures was also observed, as well as a decrease in pathways involved in tumor progression such as angiogenesis and cell proliferation. In summary, exoASO-STAT6 is a novel exosome therapeutic for selectively silencing STAT6 in TAMs, resulting in effective reprogramming of immunosuppressive macrophages to a pro-inflammatory phenotype, which in turn translates into potent single agent anti-tumor activity in multiple checkpoint refractory tumor models."

IO biomarker • Immune Modulation • Immunology • Inflammation • Oncology • CD163 • CD8 • IL12A • IL1B • STAT6 • TGFB1 • TNFA

Codiak to Present Preclinical Data Demonstrating Broad Potential Applications for Engineered Exosomes at the American Society for Gene and Cell Therapy (ASGCT) Annual Meeting (GlobeNewswire) - "Codiak BioSciences...announced that the company will present data from its engEx™ Platform at the 24th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), which is being held virtually from May 11-14, 2021. Codiak scientists will present four abstracts detailing results from numerous preclinical studies evaluating the potential utility of engineered exosomes in multiple settings, including oncology, infectious disease, gene therapy and neurology."

Preclinical • Oncology

Codiak Presents Data at AACR 2021 Demonstrating Potential of Engineered Exosomes to Enhance the Therapeutic Index of Well-Validated Cancer Immunotherapy Pathways (GlobeNewswire) - “exoASO™-STAT6…IND submission planned for H2 2021 Codiak BioSciences, Inc…reported new preclinical evidence from Codiak’s exoASO-STAT6 program…at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021…Results from multiple in vitro and in vivo studies demonstrate that exoASO-STAT6 effectively reprograms macrophages to a pro-inflammatory M1 phenotype, resulting in potent single-agent anti-tumor activity. exoASO-STAT6 exhibits a selective tropism for myeloid cells and delivered up to 12-fold more ASO to M2 macrophages in vivo than ASO administration without an exosome (e.g., ‘free’).”

IND • Preclinical • Oncology

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