Codiak BioSciences, a clinical-stage biopharmaceutical company pioneering the development of exosome-based therapeutics as a new class of medicines, today announced the initiation of patient dosing in its Phase 1 clinical trial of exoASO-STAT6, an engineered exosome precision medicine candidate designed to selectively deliver antisense oligonucleotides to disrupt STAT6 signaling in tumor associated macrophages (TAMs) and induce an anti-tumor immune response. exoASO-STAT6 is Codiak’s third clinical program and the first to evaluate a systemically administered exosome-based drug candidate.
“Targeting macrophages is the next great frontier in cancer immunotherapy and we are encouraged by the monotherapy anti-tumor activity exhibited by exoASO-STAT6 in preclinical models, which has not been observed among other approaches to date. We believe this may indicate the potential to bring transformative treatments to patients facing intractable forms of cancer,” said Douglas E. Williams, Ph.D., CEO, Codiak. “The initiation of this trial is also a significant milestone for our company, as the advancement of exoASO-STAT6 into the clinic highlights the versatility of our engineering platform. This candidate is the first of our programs to target macrophages, the first to carry a nucleic acid and the first to be administered intravenously.”
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.
TAMs promote tumor growth by exhibiting an immune suppressive M2 phenotype. Reprogramming TAMs toward a pro-inflammatory M1 phenotype may be a compelling approach to induce anti-tumor immunity. The M2 phenotype is controlled by key transcription factors such as STAT6, which have proven difficult to drug selectively in TAMs using prior approaches. Codiak plans to initially develop exoASO-STAT6 for primary cancers of the liver, where STAT6 expression has been correlated with poor survival.
In multiple in vivo preclinical studies, exoASO-STAT6 demonstrated potent single agent activity, including >90% tumor growth inhibition and 50-80% complete responses. In HCC models, exoASO-STAT6 induced significant knockdown of STAT6 mRNA, attenuated tumor growth and induced complete remission of tumor lesions in 50% of mice. This anti-tumor activity was enhanced (75% complete remissions) when exoASO-STAT6 was administered with anti-PD1 antibodies. The monotherapy activity was accompanied by remodeling of the tumor microenvironment including significant expansion of M1-like macrophages and induction of an adaptive anti-tumor immune response, enabling tumor elimination.
Source – Globe Newswire