Syntholytic™

Fully synthetic, virus-sized nanoparticles combine direct tumor cytotoxicity with immune stimulation, akin to oncolytic viruses, without the drawbacks.

  • High drug loading (> 25% m/m)
  • Evades liver and spleen clearance
  • Size enables penetration into tumor
  • Dual responsiveness for targeted accumulation and selective drug release in specific tissues and/or cells

Syntholytic enables systemic drug delivery to tumors

Current challenge

Small molecule drugs distribute systemically and are rapidly cleared. This leads to dose-limiting toxicity and poor efficacy.

Avidea's Syntholytic

Packages drugs in nanoparticles of optimal size that preferentially accumulate and release drugs in the tumor.

Benefits

Syntholytic systematically addresses key challenges of alternative technologies.

Antibody-drug conjugates (ADCs)

Key challenges

  • Indications and applications limited by target antigen expression
  • Relatively low drug loading
  • Limited to a single active agent
  • Relatively high manufacturing costs

Avidea's Syntholytic

Solutions

  • Tissue targeting through stimuli-responsiveness enables broader reach
  • High drug loading (> 25% w/w)
  • Multiple active agents possible
  • Fully synthetic, low-cost manufacturing

Liposome and PLGA particles

Conventional formulations use an empirical formulation process that results in variable and low drug loading in heterogeneous nanoparticles.

Key challenges

  • Limited improvement in efficacy as compared with drug alone
  • Limited control over drug loading as well as release
  • Manufacturing challenges including sterile filtration and release tests

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

Avidea's syntholytic is built form a “star” polymer-drug conjugate platform that enables precise, programmable drug loading in uniform nanoparticles.

Solutions

  • Targeting and controlled release improve safety and efficacy
  • Programmable, high drug loading (> 25% w/w), no variability
  • Built to enable rapid and reliable manufacturing

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.

Tumor cell targeting and controlled drug release for improving therapeutic index

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.

Slippery surface for evading capture in the blood

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.

Manufacturing advantages

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.