Codiak provides platform-validating clinical update and data from its lead engineered exosome-based therapeutics

• Codiak’s engineered exosome candidates demonstrate potential for best-in-class profile, with tumor retention and delivery to the cells of interest allowing for increased therapeutic window –
• exoSTING and exoIL-12 demonstrated favorable safety and tolerability profile at repeat doses tested and antitumor activity was observed in both injected and uninjected/distal lesions –
• Codiak has identified recommended Phase 2 dose for each program and plans to initiate Phase 2 studies for both candidates in the first quarter of 2023 –

Codiak BioSciences a clinical-stage biopharmaceutical company pioneering the development of exosome-based therapeutics as a new class of medicines, today announced platform-validating clinical data from Phase 1 trials of exoSTINGTM and exoIL-12™ and plans to advance both candidates into Phase 2 trials. In an open-label Phase 1 trial, exoIL-12 demonstrated a differentiating favorable safety and tolerability profile, with no detectable systemic exposure of IL-12 and no treatment-related adverse events, which has not previously been reported by others with recombinant IL-12. The two patients with cutaneous T cell lymphoma (CTCL) who have been treated each received multiple (>20) injections of exoIL-12 and experienced tumor regressions in both injected and non-injected lesions, including a partial response in one patient. In the open-label Phase 1/2 clinical trial evaluating exoSTING as a single agent in patients with late-stage refractory solid tumors, data across all five dose cohorts showed repeat doses of exoSTING were well-tolerated, demonstrated tumor retention with no systemic exposure of the STING agonist, and in a subset of patients, tumor shrinkage was observed in injected and uninjected lesions.

“We believe these positive datasets from our two lead programs provide further clinical validation of our engEx® Platform and the target profile for our engineered exosome therapeutic candidates. In the studies, we were able to deliver exoSTING and exoIL-12, with repeat dosing, to the tumor with a high level of specificity, no observed systemic exposure or associated toxicity, and an enhanced therapeutic index–while demonstrating tumor shrinkage in both injected and uninjected lesions,” said Douglas E. Williams, Ph.D., President and Chief Executive Officer of Codiak. “STING and IL-12 have been challenging targets that have historically been hampered by very toxic side effects, but we believe our approach may enable best-in-class therapies with favorable safety profiles. Based on these findings, we have identified a recommended Phase 2 dose for both programs. We plan to initiate a Phase 2 study of exoSTING in bladder cancer and a Phase 2 study of exoIL-12 in an expanded group of tumor types in the first quarter of 2023.”

exoIL-12 Data and Development Plan

The Phase 1 clinical trial was designed in two parts, with the data from the healthy volunteer portion of the study reported last year. In the CTCL portion of the study, two patients with early stage CTCL whose disease progressed on prior therapy have been treated as of the June 10, 2022, data cut-off. Each patient has received more than 20 injections of exoIL-12 (6.0 μg) across multiple lesions. Duration of treatment has been greater than six months, and no treatment-related adverse events Grade 3 or higher or SAEs were observed, and no dose modifications were required.

exoIL-12 demonstrated improvement in overall tumor burden, as measured by mSWAT, and lesion severity, as measured by CAILS, in both patients treated. Patient 001 had a total of 5 skin lesions, 3 of which were injected and exhibited a partial response, as per mSWAT (a registrational endpoint) with a 61% decrease in disease burden. Improvement in CAILS scores for all skin lesions, both injected and uninjected, ranged from 20-80%. All skin lesions have resolved, and additional injections were deemed unnecessary by the treating physician. The patient remains on study. Patient 002 had 3 skin lesions, 2 of which were injected (20 injections to date) and has demonstrated a 43% decrease in disease burden. Improvement in CAILS scores have been seen ranging from 30-50% for all lesions, both injected and uninjected. This patient remains on study and continues to receive exoIL-12 injections.

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. In contrast, previous rIL-12 clinical studies showed dose-dependent systemic exposure with dosages of 5 and 12 μg resulting in Cmax plasma levels of approximately 15 to 45 pg/ml within 6 to 12 hours after dosing.1

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.

exoSTING Data and Development Plan

Data as of June 10, 2022, are being reported from all five escalation dose cohorts (0.3 mcg, 1.0 mcg, 3.0 mcg, 6.0 mcg and 12.0 mcg) enrolled in the Phase 1/2 study. Dosing is still underway in the 12.0 mcg cohort and all patients continue to be followed. Trial participants (n=23) were administered exoSTING intratumorally, and nearly all had received at least two prior therapies prior to study entry with most (65%) having progressed on checkpoint inhibitors.

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. Treatment-related serious adverse events (TRSAE) were observed in three patients (2 patients with Grade 2 cytokine release syndrome and 1 patient with Grade 1 pyrexia). All patients who experienced a TRSAE were retreated and remained on study without additional SAEs.

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. Paired tumor biopsies available from Cohorts 1-4 show evidence of an adaptive immune response, including consistent increases in CD-8 effector T-cells and PD-L1 in the tumor micro-environment.

Signs of antitumor activity were observed with tumor shrinkage in injected as well as distal, non-injected tumors.

The data support advancing exoSTING into Phase 2 development, particularly in early-stage disease where combination with immunotherapy may lead to enhanced activity. 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.

“This is a critical milestone for Codiak because we met our objectives for the Phase 1 studies of exoSTING and exoIL-12 and the data support the differentiated target profile we had hoped to unlock with our engineered exosome platform. What is remarkable is that these exosomal formulations are demonstrating results that free STING agonists and systemic IL-12 were unable to achieve due to significant limitations in safety and therapeutic index, opening up the possibility that these two promising targets can benefit cancer patients,” said David Mauro, M.D., Ph.D., Chief Medical Officer of Codiak. “We are enthusiastic about moving these programs into Phase 2 early next year while continuing to monitor patients from ongoing studies and submitting data to upcoming medical meetings.”

Source – Globe Newswire