Benzinga | Nov 16, 2021 06:48AM EST

Codiak Reports Initial Data For exoSTING Phase 1/2 Trial

-- exoSTING resulted in localized STING pathway activation and dose-dependent immune activation --

-- Intratumoral administration of exoSTING was well tolerated and demonstrated tumor retention, no systemic exposure to STING agonist, and in a subset of patients, tumor shrinkage in injected and distal non-injected lesions --

-- Data on objective response rate and recommended Phase 2 dose selection for expansion anticipated 1H 2022 --



-- Codiak to host conference call and webcast today at 8:00 am ET --

CAMBRIDGE, Mass., Nov. 16, 2021 (GLOBE NEWSWIRE) -- Codiak BioSciences, Inc. (NASDAQ:CDAK), a clinical-stage biopharmaceutical company focused on pioneering the development of exosome-based therapeutics as a new class of medicines, today 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.

"We are excited to see that the initial foundational data from our exoSTING program are consistent with the pharmacologic activity that we observed with the candidate preclinically, and point to a differentiated mechanism of action afforded by the engineered exosome-based delivery of the STING agonist," said Doug Williams, PhD, CEO of Codiak. "The targeted delivery and tumor retention observed so far appear to effectively engage the STING pathway, and at tested doses, exoSTING was well tolerated and showed initial signals of clinical activity. These data also reinforce our conviction that our engineering platform enables the specific design of therapeutic molecules with desired attributes to effectively modulate important targets that have not been successfully drugged before."

In the first three dose cohorts of trial participants treated with exoSTING in this ongoing dose-escalation study, evidence of local STING pathway activation and stimulation of both innate and adaptive immune responses were observed at all tested doses (0.3 mcg, 1.0 mcg, and 3.0 mcg). Intratumoral injection of exoSTING did not lead to systemic exposure to the STING agonist and was well tolerated at all dose levels tested. Additionally, pharmacodynamic data indicated that intratumoral administration of exoSTING was >100-fold more potent than data reported in prior published STING agonist clinical studies. Analysis of blood cells after exoSTING dosing showed the migration of activated cells from the tumor, and in some subjects, substantial induction of Interferon Stimulated Genes (ISG), which are involved in interferon response and activation of antigen presenting cells (APCs). Tumor shrinkage of injected and non-injected lesions were noted in a subset of subjects.

exoSTING is one of the first engineered exosome therapeutic candidates to be evaluated in humans and one of two Codiak programs currently in clinical development. exoSTING was engineered with the company's proprietary engEx(tm) Platform and designed to deliver Codiak's proprietary STING (Stimulator of Interferon Genes) agonist specifically to tumor-resident APCs to locally activate the innate immune response and to generate an adaptive immune response by presenting tumor antigens to T cells.

The STING pathway is a validated drug target, yet therapeutic development has been generally limited by lack of tumor retention, tolerability issues due to systemic exposure to the agonist and T-cell ablation in the tumor at higher agonist doses, resulting in the inability to effectively engage the pathway. In preclinical models of exoSTING, the targeted delivery of a STING agonist to tumor resident APCs promoted localized innate immune activation, T cell attraction and expansion in the tumor, and the development of systemic immunity not observed with a STING agonist delivered without exosomes (e.g., "free").

Initial Data from Dose Cohorts 1-3

The initial data are being reported from the first three ascending dose cohorts (0.3 mcg, 1.0 mcg, and 3.0 mcg) enrolled in the Phase 1/2 study. Trial participants (n=11) were administered exoSTING intratumorally and all subjects had received at least two prior therapies prior to study entry with most (73%) having progressed on checkpoint inhibitors.

Plasma pharmacokinetic (PK) measurements of subjects 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 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.

Blood biomarker assessments conducted post dosing showed evidence of dose-dependent activation of the STING pathway and Type I INF induction along with CXCL10, indicating activation of the innate immune response. Paired tumor biopsies available from two subjects showed evidence of an adaptive immune response and CD8 effector T cell infiltration into the tumor, as well as an increase in PD-L1 expression.

Finally, in subjects evaluable for early signs of antitumor activity (n=8), tumor shrinkage was observed in injected as well as distal, non-injected tumors, in a subset of subjects.

Enrollment in cohorts 4 (6 mcg) and 5 (12 mcg) of the exoSTING trial is ongoing. Data from all five cohorts including objective response data are expected in the first half of 2022, which will enable identification of a recommended Phase 2 dose.

exoSTING Development and Ongoing Phase 1/2 Clinical Trial

The Phase 1/2 dose escalation clinical trial of exoSTING is designed to investigate safety, tolerability, pharmacological activity, and objective tumor response in patients with advanced/metastatic, recurrent, injectable solid tumors, with a focus on tumors likely to be enriched in APCs. 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.

About exoSTING(tm)

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. Codiak believes that exoSTING has the potential to overcome certain limitations of free STING agonists, and to enhance the therapeutic index and selectivity of delivery to desired cells in the tumor microenvironment.