exoASO-STAT6

P1, N=9, Terminated, 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

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.

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.

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).

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.