Advancing a New Class of Medicines

Company to Watch – NeuBase Therapeutics

In the second of four features on NeuBase Therapeutics, Big4Bio spoke with Founder and CEO Dietrich Stephan and CFO Todd Branning about the company’s precision genetic medicine technology and pipeline, partnering and financing activities, and plans moving forward.

By Marie Daghlian

Todd Branning, chief financial officer of NeuBase Therapeutics, joined the company in January 2022. Having worked across a spectrum of life science companies over the past 20 years, he was looking for something in his next venture that would be unique and differentiated in terms of the science.


“That is absolutely present here at NeuBase, and I was excited to join and become a part of the journey,” he says.

NeuBase’s precision genetic medicine technology is called PATrOL, or peptide-nucleic acid antisense oligonucleobase, a platform that is in a class of its own and a unique approach to drugging the genome to treat disease, both rare and common. Not only can NeuBase’s synthetic PNAs target the genome with single base precision, but the platform has also been engineered to be able to deliver the therapeutic in a patient-friendly manner.

The company’s PNAs are comprised of nucleobases that have been engineered to be highly selective to binding the target DNA or RNA mutation to minimize off-target effects, have a neutral-charged backbone to confer high-binding affinity and drug-like properties, and the platform has been engineered to enable systemic delivery to achieve broad tissue distribution or to be targeted.

While NeuBase believes its platform can be applied to any genetic disease, it has started with three programs, all of which are in the preclinical stage. The company’s lead program targets myotonic dystrophy type 1, or DM1, which is an inherited form of muscular dystrophy that’s characterized by a repeat expansion of trinucleotides in the DMPK gene. The expansion of the genetic sequence leads to myotonia, weakness in smooth and skeletal muscle, including cardiac muscle, and cognitive defects that manifest over time. A shortened lifespan is the ultimate consequence of those that suffer from this disease.

“Because of the design of our platform and the design of our PNAs, this is an excellent target for us to pursue because we can go in with our technology and address the repeat expansion sequence that leads to the disease,” Branning says. “We believe we can correct that with our technology.”

NeuBase plans to submit an Investigational New Drug (IND) application to the FDA for this program by the end of the year and begin human studies in 2023.

NeuBase’s second program targets Huntington’s disease, an inherited neurodegenerative disorder also characterized by a repeat expansion driven by the HTT gene that results in the creation of mutant huntingtin proteins, which impact the deep brain and result in cognitive deficits and defects that lead to movement disorders and other effects that shorten a person’s lifespan.

Finally, last summer the company started work on an oncology program looking at mutations in the KRAS gene, specifically G12D and G12V mutations, which are leading causes of several cancerous tumors that can result from malfunctions in this gene. Right now, NeuBase scientists are optimizing candidates that could address the mutations.

Recently reported preclinical data on the lead DM1 program was met favorably by investors, because it showed that “in a nutshell, it works,” says Dietrich Stephan, founder and CEO of NeuBase. “No one has ever brought peptide nucleic acid technology, this chemistry, into the clinic, and in the marketplace before.”

“What we showed—the defining feature of that data set—was a single intravenous injection into the gold standard animal model with this disease resolved the molecular defects and the functional deficits in the skeletal muscle, and was durable for at least six weeks after a single dose, the latest time point we tested,” Stephan added. “We are evaluating the option to do this via a more patient-friendly route in a subcutaneous manner. So, I’d say it was really a pivotal data set for us.”

Branning added that the investment community had been waiting for some data, especially since NeuBase has a differentiated approach to treating DM1. Now they have data, very good data that the approach works. “We showed some data on muscle relaxation that others have not shown,” he said. “I see that it’s unique and differentiated. Obviously, there’s more work to be done, but it provided initial validation of the overall platform.”

NeuBase’s headquarters in Pittsburgh, Pennsylvania. The company also has an office in Cambridge, Massachusetts.

The most important near-term milestone will be the filing of an IND application in DM1, but the company expects to release other important data readouts along the way, including PK ADME work in wild type mice, PK/PD work in transgenic murine models, and GLP toxicology studies that will be necessary to move to the IND submission.

When asked about partnering, Branning says there’s widespread interest among the pharma industry in its platform, technologies, and capabilities to address numerous rare and common diseases.

“The capability of our platform in terms of the numbers of genes and diseases that we could develop against is too many for one company of any size,” says Stephan. “So, we’ve been excited about the enthusiasm on the part of big pharma, for us to source innovation to them, to address undruggable targets that are interesting to them. Remember nearly every disease is genetic, and we have the potential to drug any gene.”

Biotech companies always need cash, and NeuBase is no different. Branning says the company is in a reasonable position right now relative to its cash, but given the challenging market environment, it is looking at ways to extend its cash where it can, such as identifying and acting on opportunities to delay or defer some expenditures.

“We think that’s entirely prudent in the market that we currently face. Having said that, we will need capital,” Branning says. “In the near term, we’ve got enough funds to get us through the IND submission at the end of this year, and to probably start clinical work in the early part of next year. We’re looking at a range of options and alternatives on how to raise additional capital for the company. I’m confident that we’ll be able to get additional capital to support the progress of our programs. People are really looking for good high quality ideas and we think that we are certainly one of those with a differentiated platform in technology. As you’ve seen with the data that we recently reported and the response to that, there’s a lot of interest in NeuBase, and we believe that interest will continue as our story develops.”

Branning is excited to be part of the NeuBase story. “What I’ve learned and what I’ve seen, and where we’re at right now, all suggest to me that, not only are we differentiated and unique, but our time is now,” he says. “We are embarking on a period where this is not something that is still a long way out in the future in terms of when the potential of this might be realized. I really believe it’s here and now and in front of us. There’s work to be done for sure, but it’s exciting to have joined when I did with respect to where the company is in its life cycle, and it’s just a great time for us right now. The present is really bright.”


NEXT: Podcast with NeuBase CEO Dietrich Stephan

This is part of the Big4Bio Company to Watch program for April 2022: NeuBase Therapeutics
For more information on the series, click here