Fully synthetic, virus-sized nanoparticles combine direct tumor cytotoxicity with immune stimulation, akin to oncolytic viruses, without the drawbacks.
Small molecule drugs distribute systemically and are rapidly cleared. This leads to dose-limiting toxicity and poor efficacy.
Packages drugs in nanoparticles of optimal size that preferentially accumulate and release drugs in the tumor.
Conventional formulations use an empirical formulation process that results in variable and low drug loading in heterogeneous nanoparticles.
Many particle drug delivery technologies are rapidly cleared from the blood by spleen and liver antigen presenting cells (APCs) and/or are too large for efficient tumor extravasation.
Avidea's syntholytic is built form a “star” polymer-drug conjugate platform that enables precise, programmable drug loading in uniform nanoparticles.
Syntholytic comprises flexible polymer arms that prevent capture by liver and spleen APCs and are of an optimal, small (~30 nm) size to promote tumor entry.
Cytotoxic and immunostimulatory drugs often suffer from dose-limiting toxicities. Syntholytic solves this challenge in two ways using dual responsiveness. First, the syntholytic evades APC capture at physiologic pH 7.4 but undergoes morphological changes that promote cellular uptake at reduced pH in the tumor. Second, drug molecules are linked to bonds that are selectively degraded within the tumor (or inside specific cellular compartments), providing dual mechanisms for tumor selectivity.
Syntholytic comprises proprietary polymer arm compositions that prevent blood clearance by APCs and enable repeated administration without inducing antibodies. This provides major advantages over oncolytic viruses and other therapies that are limited by anti-vector antibodies.
Syntholytic, as the name suggests, is comprised entirely of biocompatible, synthetic components providing major cost savings as compared with recombinant technologies.
Uniform nanoparticle compositions achieved with syntholytic simplifies manufacturing release testing.
Finally, syntholytic comprises uniform ~30 nm particles that can be sterile filtered without material loss, addressing an otherwise major manufacturing challenge.