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3:54 PM
Aug 01, 2019
 |  BC Innovations  |  Product Development

NeuBase takes antisense oligos to more targets in more places

How NeuBase’s antisense oligo platform broadens the modality’s therapeutic horizons

Newcomer NeuBase Therapeutics is re-engineering antisense oligos to access a broader range of targets, while simultaneously solving the modality’s dosing and delivery issues.

With three approvals since the start of 2016, antisense oligonucleotides (ASOs) have started to hit their stride, yet first-generation technologies are limited on multiple fronts.

Most ASOs only target linear RNA, which means they fail to bind the more complex structures often assumed by mutant, disease-causing RNAs. And ASOs don’t cross the blood-brain barrier, which has meant that Biogen Inc.’s spinal muscular atrophy therapy Spinraza nusinersen must be delivered intrathecally.

NeuBase aims to address those issues, plus several others, with its Peptide-nucleic acid AnTisense OLigonucleotide, or PATrOL, platform.

Founded by serial entrepreneur and CEO Dietrich Stephan, NeuBase Therapeutics Inc. made its trading debut on NASDAQ through a reverse merger on July 18, just 11 months after launching.

Stephan told BioCentury the biotech took advantage of an RNA-hungry market to eschew the more traditional VC financing route, enabling it to hand pick its board without restrictions. It attracted former Global Head of Innovation at Johnson & Johnson and current Vividion Therapeutics Inc. CEO Diego Miralles, as well as Franklyn Prendergast, who served on the board of Eli Lilly and Co. from 1995-2017 (see SideBar: “NeuBase Takes Control”).

On July 30, the company added more big names to its roster when former National Cancer Institute Director Samuel Broder and serial entrepreneur George Church, a professor of genetics at Harvard Medical School, joined its SAB.

A key differentiator of NeuBase’s PATrOL platform is its collection of double-sided nucleic acid bases, which are responsible for the oligos’ ability to bind new target types. These “bifacial” bases can bridge two strands of RNA, allowing them intercalate into a variety of folded RNA structures, not just bind to linear strands.

The bases can also bind DNA, offering an entirely different mechanism for regulating protein expression.

“Now we can target regions of genes like a promoter with an ASO.”

Dietrich Stephan, NeuBase Therapeutics Inc.

The biotech’s platform also improves delivery and dosing via a novel trafficking ligand and streamlines manufacturing via tweaks to the molecules’ peptide backbones.

The trafficking ligand renders the oligos blood-brain barrier penetrant, solving the CNS delivery problem, and transports the molecules directly into the cytoplasm. The latter avoids the loss of therapy that normally occurs after endosomal uptake, and could enable lower dosing.

The components of PATrOL springboard off work by NeuBase’s scientific founder and CSO Danith Ly at Carnegie Mellon University, where he remains a professor of chemistry.

NeuBase is applying PATrOL first to Huntington disease (HD) and myotonic dystrophy, and plans to take a program into the clinic in at least one of those indications in 1Q21. It also has a handful of earlier stage oncology programs.

The biotech has maintained about a $66 million market cap since it began trading, and Stephan said it has 15-18 months of runway.

Sidebar: NeuBase takes control

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