exoIL-12 / 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

Part B: A Phase 1/2a Study of CDK-003 in Patients With Cutaneous T-Cell Lymphoma (CTCL). (clinicaltrials.gov) - P1/2 | N=2 | Terminated | Sponsor: Codiak BioSciences | N=30 ➔ 2 | Trial completion date: Jan 2024 ➔ Aug 2022 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2023 ➔ Aug 2022; PK/PD from two patients plus the healthy volunteer data confirmed the RP2D and manageable safety profile. Proceeding to Phase II did not require additional data from this Phase I Dose-Finding study.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

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 | N=30 | NCT05156229 | Sponsor: Codiak BioSciences | "exoIL-12 demonstrated improvement in overall tumor burden, as measured by mSWAT, and lesion severity, as measured by CAILS, in both patients treated....Plasma pharmacokinetic (PK) measurements of both healthy volunteers and patients that received exoIL-12 showed no systemic exposure with levels of IL-12 below the limit of quantification....Data from the CTCL patients further validate 6 mcg as the intended dose for Phase 2 development. Codiak intends to conclude the current study in the UK and transition to a U.S. Investigational New Drug (IND) application. Codiak anticipates initiating a Phase 2 trial during the first quarter of 2023 in patients with cutaneous malignancies responsive to rIL-12 in studies historically, including CTCL, Kaposi’s sarcoma, Merkel cell carcinoma, and squamous cell carcinoma – each orphan cutaneous diseases treated by the same physicians, where local treatment is common."

New P2 trial • P1 data • Cutaneous T-cell Lymphoma • Hematological Malignancies • Kaposi Sarcoma • Lymphoma • Merkel Cell Carcinoma • Non-Hodgkin’s Lymphoma • Oncology • Squamous Cell Carcinoma

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

Part B: A PHASE 1/2a, STUDY OF SAFETY, TOLERABILITY, PHARMACOKINECTS AND PHARMACODYNAMICS OF CDK-003 (exoIL-12) IN PATIENTS WITH CUTANEOUS T-CELL LYMPHOMA (CTCL) (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Codiak BioSciences | Phase classification: P1 ➔ P1/2

Phase classification • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Part B: A PHASE 1, DOSE ESCALATION STUDY OF CDK-003 (exoIL-12) IN PATIENTS WITH CUTANEOUS T-CELL LYMPHOMA (CTCL) (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Codiak BioSciences

Clinical • New P1 trial • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

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

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] Randomized placebo-controlled Phase 1 trial in healthy volunteers investigating safety, PK and PD of exoIL-12 - a novel engineered exosome therapeutic candidate (AACR 2021) - "Studies of recombinant IL-12 conducted by others in healthy volunteers at comparable dose levels to the present study resulted in dose dependent systemic IL-12 exposure as well as IFNγ and IP-10 production and common adverse events such as fever, chills, myalgia, headache, and muscle pain. In contrast, exoIL-12 demonstrated a favorable safety and tolerability profile with no treatment-related adverse events and no systemic IL-12 exposure. Local IL-12 levels in the skin as well as pharmacodynamic data from blood and skin samples will be presented."

Clinical • P1 data • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • IFNG • IL12A

Codiak Presents Data at AACR 2021 Demonstrating Potential of Engineered Exosomes to Enhance the Therapeutic Index of Well-Validated Cancer Immunotherapy Pathways (GlobeNewswire) - “exoIL-12™…patient data readout expected by YE 2021…New pharmacodynamic data presented at AACR 2021 show no systemic IFN-γ production, which may further explain the favorable safety and tolerability of exoIL-12. Pharmacodynamic data from skin punch biopsies showed detectable levels of exoIL-12 in the skin at the 6.0 μg dose as much as 24 hours post injection, indicating retention at the injection site and prolonged activation of the IL-12 signaling cascade. Based on these findings, the 6.0 μg dose level has been selected for the second portion of the Phase 1 trial currently underway, where the safety and efficacy of exoIL-12 will be evaluated following repeat doses into the lesions of patients with early-stage CTCL.”

P1 data • PK/PD data • Oncology

"IL12 wrapped in a blanket CT114 - Randomized placebo-controlled Phase 1 trial in healthy volunteers investigating safety, PK and PD of exoIL-12 - a novel engineered exosome therapeutic candidate #AACR21" (@PDRennert)

Clinical • P1 data • 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

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

Codiak to Present Data from Two Novel Engineered Exosome Therapeutic Candidate Programs at the American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - “Codiak BioSciences, Inc…announced that the company will present data from two of its programs evaluating engineered exosome therapeutic candidates for the treatment of cancer at the upcoming virtual American Association for Cancer Research (AACR) Annual Meeting 2021…‘We expect exoASO-STAT6 will be our third clinical program with a planned Investigational New Drug (IND) filing later this year.’”

P1 data • Preclinical • Oncology

Codiak Reports Additional Positive Phase 1 Results for exoIL-12 Confirming Local Pharmacology and Dose Selection for Safety and Efficacy Trial in Early-Stage Cutaneous T Cell Lymphoma (CTCL) Patients (GlobeNewswire) - P1, N=25; "Codiak BioSciences, Inc...announced pharmacodynamic (PD) activity results from the healthy volunteer portion of its randomized, placebo-controlled, double-blind Phase 1 trial of the company’s clinical candidate, exoIL-12. Analyses of skin punch biopsies bordering the subcutaneous injection site of exoIL-12 revealed local retention of immunologically detectable IL-12 at the injection site, and localized pharmacological activity as measured by levels of the T cell attractant chemokine, IP-10, in the skin. IL-12 was not detected in plasma at any dose of exoIL-12 tested and plasma IP-10 was only detectable at the highest, 12 μg dose....Safety, biomarker and preliminary anti-tumor efficacy results are anticipated by the end of 2021."

P1 data • Cutaneous T-cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Codiak Reports Positive Initial Phase 1 Results for exoIL-12 Demonstrating Tolerability and Absence of Systemic IL-12 Exposure in Healthy Volunteers (GlobeNewswire) - P1, N=N/A; "Codiak BioSciences...today announced that the primary objectives were met in the initial part of its Phase 1 trial, which evaluated a single ascending dose of exoIL-12 in healthy volunteers...'We’re looking forward to advancing exoIL-12 into the multi-dose part of the study in cutaneous T cell lymphoma patients and presenting the detailed results from the healthy volunteer part of this study at an upcoming medical conference.'...The company intends to use these results to identify an optimal pharmacological dose to carry forward into the second part of the trial, which is on track to begin in Q1 2021 and will evaluate repeat dosing of exoIL-12 in patients with early-stage cutaneous T cell lymphoma (CTCL)."

P1 data • Cutaneous T-cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Phase update (Businesswire) - Preclinical➔P1, CTCL

Phase shift • Cutaneous T-cell Lymphoma • Non-Hodgkin’s Lymphoma

Exosome surface display of IL-12 results in tumor-retained pharmacology with superior potency and limited systemic exposure compared to recombinant IL-12. (PubMed, Mol Cancer Ther) - "This work demonstrates that tumor-restricted pharmacology of exoIL-12 results in superior in vivo efficacy and immune memory without systemic IL-12 exposure and related toxicity. ExoIL-12 is a novel cancer therapeutic candidate that overcomes key limitations of rIL-12 and thereby creates a therapeutic window for this potent cytokine."

Journal • Oncology

New Publication in Molecular Cancer Therapeutics Highlights Data from Preclinical Development of exoIL-12 for the Treatment of Cancer (GlobeNewswire) - "Codiak BioSciences, Inc...announced the online publication of a new manuscript, Exosome surface display of IL-12 results in tumor-retained pharmacology with superior potency and limited systemic exposure compared to recombinant IL-12, in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research."

Preclinical • Oncology

[VIRTUAL] Exosome surface display of IL-12 results in tumor-retained pharmacology with superior potency and limited systemic exposure (SITC 2020) - "Conclusions This work demonstrates that tumor-restricted pharmacology of exoIL-12 results in superior in vivo efficacy and immune memory without systemic IL-12 exposure and related toxicity. exoIL-12 is a novel cancer therapeutic candidate that has the potential to overcome key limitations of rIL-12 and thereby create a therapeutic window for this potent cytokine."

Oncology • CD8 • IFNG • IL12A

[VIRTUAL] Exosome surface display of IL-12 results in tumor-retained pharmacology with superior potency and limited systemic exposure (SITC 2020) - "Conclusions This work demonstrates that tumor-restricted pharmacology of exoIL-12 results in superior in vivo efficacy and immune memory without systemic IL-12 exposure and related toxicity. exoIL-12 is a novel cancer therapeutic candidate that has the potential to overcome key limitations of rIL-12 and thereby create a therapeutic window for this potent cytokine."

Oncology • CD8 • IFNG • IL12A

Codiak Presents Preclinical Data at SITC 2020 Demonstrating Potential of engEx Engineered Exosomes to Stimulate Targeted, Integrated Anti-Tumor Immunity (GlobeNewswire) - "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 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....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."

P1 data • Preclinical • Cutaneous T-cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Codiak Initiates Subject Dosing in a Phase 1 Clinical Trial of exoIL-12 for the Treatment of Cancer (Businesswire) - “Codiak BioSciences, Inc…announced the initiation of subject dosing in its Phase 1 clinical trial of its novel exosome therapeutic candidate, exoIL-12…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…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.”

New P1 trial • P1 data • Trial status • Cutaneous T-cell Lymphoma • Hematological Malignancies • Oncology