A high throughput platform for intracellular delivery of impermeable drug molecules and molecular probes to enable a new generation of screening assays

The National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health awarded Portal Biotechnologies $1.215 million on September 1, 2026, under CFDA 93.350 (National Center for Advancing Translational Sciences) to develop a high-throughput screening platform for intracellular delivery of impermeable drug molecules and molecular probes.

Portal Biotechnologies is advancing its Galaxy system, a mechanoporation-based platform that uses disposable cartridges to enable multiplexed intracellular delivery of diverse biomolecules in cell-based screening assays. The technology addresses early-stage drug discovery bottlenecks by enabling screening of compounds in live cells before initiating expensive medicinal chemistry campaigns, thereby reducing the risk of pursuing compounds that ultimately fail biologically. The system also enables novel assays to understand drug-target interactions. The company has progressed the Galaxy prototype through early-stage development and intends to advance it further under this award.

Performance is located in Watertown, Massachusetts. The period of performance extends from September 1, 2026, through August 31, 2028. This is a Project Grant assistance type.

Abstract

Drug discovery is a long, challenging, and expensive process, driven by extensive preclinical testing and a high failure rate at the clinical trial stage of development. Early holdups in drug discovery include limited ability to probe inside cells to understand the underlying disease biology and understand drug-target interactions. Current systems for screening potential drugs ("hits") often struggle with permeability issues. Medicinal chemistry (MED chem) campaigns are expensive and time consuming, and often used for molecules that ultimately fail biologically. Robust intracellular delivery technologies could enable HIT verification prior to resource intensive MED chem campaigns. Without improved processes, the success rate for drug discovery remains low with many promising compounds failing to make IT to the clinic, while many ultimately unsuccessful molecules are not excluded early-on. An improved method to DE-risk early "hits" prior to MED chem work has the potential to transform early-stage drug discovery. Portal biotechnologies is revolutionizing drug discovery by leveraging our high throughput screening galaxy prototype to dramatically improve biological insights early in the drug discovery process. Our approach enables screening of compounds in cell-based systems before initiating expensive MED chem campaigns. IT can also enable novel assays by delivering a diversity of molecular probes to understand drug-target interactions in a live cell. The core of our galaxy system is a disposable cartridge that uses our mechanoporation technology to enable multiplexed, intracellular delivery of diverse biomolecules. Our technology is flexible, gentler on cells, and provides more information - while also offering cost savings. We have progressed the galaxy prototype through early-stage development, and intend to build on our initial success by now adapting the galaxy prototype for broad adoption, ensuring compatibility with a variety of liquid handlers that are commonly used (aim 1) and develop general protocols that are compatible with novel intracellular assays for drug-target interaction and intracellular staining that can accelerate drug discovery (aim 2). Successful completion of this proposed project will result in the development of portal's galaxy system, a groundbreaking platform for early-stage compound screening in complex cell-based systems. This technology will advance the field of drug discovery by enriching the biological and mechanistic data available early in the drug discovery pipeline and thereby further discriminate and DE-risk in favor of compounds that can succeed in the clinic.