Science

Untapping Potential

There is an urgent need for improved viral vector technology to meet the needs for the wide array of gene therapies in early-stage development, which FDA estimates will lead to 20 approved products per year by 2025.1  Conventional AAVs offer little-to-no therapeutic window, requiring high doses that are associated with substantial toxicity from off-target effects. This risk/benefit imbalance has resulted in numerous development setbacks, delays, disappointments, and lost investment. When dosed intravenously, proprietary Voyager capsids may fill this need, as they have been shown to penetrate the blood-brain barrier in non-human primates and achieve widespread transgene expression that is superior to conventional AAV serotypes.2

Powering the Next Chapter

Voyager’s world-class vector engineering expertise is creating screening efficiencies that may accelerate scientific breakthroughs. The Company’s TRACERTM screening platform is identifying improved vectors selected to target desired cells and tissues with greater specificity, at lower doses, and with reduced risk of off-target effects compared to conventional AAV. Initial non-human primate data demonstrate TRACER-derived capsids have enhanced tropism for the CNS and cardiac muscle, and further screening is intended to identify capsids with enhanced tropism for other tissue and cell types that may enable single-dose treatment for a broad spectrum of diseases.2,3

TRACERTM: Tropism Redirection of AAV by Cell-type-specific Expression of RNA

TRACER identified several blood-brain barrier (BBB) penetrant capsids.

The first of several TRACER screening campaigns identified novel capsids targeting desired cells and tissues with greater specificity, at lower doses, and with fewer off-target risks than conventional AAV serotypes in non-human primates.2,3

TRACER capsid demonstrates unprecedented CNS transduction in non-human primates.

The TRACER platform has produced a number of capsids with substantially enhanced BBB penetration and transgene expression throughout the CNS, including a capsid from the first TRACER NHP campaign that achieved 1,000- to 10,000-fold increased expression compared to AAV9 across a wide array of brain regions when dosed intravenously.3

TRACER can be designed to target tissues with high specificity.

A TRACER capsid identified through an initial screening campaign has demonstrated enhanced cardiac muscle transduction and significant dorsal root ganglia detargeting compared to AAV9, which may help reduce toxicities.3

TRACER can be targeted to identify capsids for a diverse set of tissue and cell types.

The TRACER platform can select for capsids enhanced for any desired tropism. TRACER has produced capsids with enhanced targeting of the CNS and cardiac muscle and holds promise for producing capsids with enhanced tropism for skeletal muscle, eye, liver, and other tissues.

Vectorized Antibodies

Leveraging novel TRACER capsids and systemic delivery, Voyager’s vectorized antibody platform is capable of delivering payloads to the brain that express both secreted antibodies and intrabodies, which act within cells such as neurons. The diversity of vectorized antibody payloads create the potential to engage targets that would otherwise be undruggable or unreachable.

1https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-and-peter-marks-md-phd-director-center-biologics
2 Mol Ther Methods Clin Dev. 2020 Dec 23;20:366-378.
 3 Nonnenmacher, et al. “RNA-driven Evolution of AAV Capsid Libraries Identifies Variants with High Transduction Efficiency in Non-Human Primate Central Nervous System.” ASGCT 2021.

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