Tackling memory loss: Nia Therapeutics

I am pleased to announce the launch of Neurotech Nexus; a series where I will be sharing conversations with leaders in the Neuro space. We will be talking about all things Neuro, from technology to investment to regulatory and many more topics.

This is for the curious minds who want to learn from pioneers in the Neurotech space.

For the 1st in the series, I was able to grab some time with Dan Rizzuto , CEO of Nia Therapeutics in the US 🇺🇸. They are developing Brain stimulation therapies to treat memory loss caused by brain injury and degenerative diseases such as Alzheimer's. We talked through the Nia journey, their technology and the challenges they have had along the way. Dan also shared some solid advice for founders at the early stages of their startup journey.

Tell me a bit about your background and your journey to where you are today.

"I'm a neuroscientist by training. I completed my PhD at Brandeis University, where I studied the neuroscience of human memory. At the time, this field was still in its early stages, and my advisor, Mike Kahana, was one of the pioneers in conducting careful behavioural studies of memory while recording brain activity from patients undergoing invasive brain recordings. Together, we built a substantial body of literature on the electrophysiological basis of memory. It was a wonderful experience, but I felt the need to get closer to therapeutic development and patient impact.

So, I went to Caltech for my postdoc, where I focused on translational neuroscience, particularly on building neuroprosthetics for paralyzed patients. This was about 20 years ago, long before Elon Musk became known for his work in the neurotech space. However, even at Caltech, I felt that we were still somewhat distant from the clinic. I wanted to be closer to actual therapeutic applications, so I transitioned into the industry. I joined a company called Northstar Neuroscience in 2007, where I focused on developing implantable neurostimulation therapies for depression.

Working at Northstar Neuroscience was an incredible experience. I witnessed firsthand the impact that a revolutionary therapy can have on a patient's life. Seeing a patient who had been practically bedridden for over a decade due to depression, suddenly able to lift the weight of depression through brain stimulation therapy, was profound. It was then that I realized that I wanted to be in the clinical development of neurotechnology.

For the past 20 years, I have been dedicated to developing various neurotechnologies. And in 2014, I received a call from my former advisor, Mike Kahana, who by then was at the University of Pennsylvania. He informed me that he had just received $20 million from DARPA to pursue a project that we had always dreamed about: using brain stimulation to modulate memory. This was an incredible opportunity to move beyond the basic research of memory and to actually develop a memory therapy.

I immediately knew that I had to seize this opportunity. So, I left Seattle and moved to Philadelphia to join Mike at Penn and lead the project called Restoring Active Memory, funded by DARPA. Together, we developed this memory technology, and it has been an amazing journey."

Why get into neuroscience in the beginning, even before neurotechnology and seeing the impact firsthand?

"I was attracted to very challenging problems with incredible teams, and I just happened to find that in neuroscience. There are few more challenging problems than understanding the brain, and there are an incredible number of people trying to do just that; as audacious as that is.  I just happened to connect with people in neuroscience, and that ignited my interest, which then developed into neurotechnology development.

After I completed my PhD I asked myself, "what can I do with a PhD in neuroscience?" This was 20 plus years ago, before the explosion of neurotechnology companies. Nowadays, it's second nature for graduate students to say, "Oh yeah, I'm going to join a neurotech company." But these companies weren't around when I was in graduate school. So, the developments were slower, but I'm very happy with where I have wound up."

Tell me about Nia Therapeutics. What product are you guys developing, what problem does it solve and how does it work?

"Nia Therapeutics is developing brain stimulation therapies for treating memory loss. This work stems from my graduate studies with Mike Kahana at the University of Pennsylvania. Mike had the initial insight, based on all the foundational work he had done at Brandeis and then at Penn, that we could decode human memory states. We could predict whether somebody is in a good memory state and will remember the information they're currently learning, or if they're in a poor memory state and won't remember that information.

This in itself is incredible. Mike then realized that we could build a therapy on top of this brain decoding technology. So, that's exactly what we did. We developed a closed-loop neurostimulation therapy for memory. Using artificial intelligence, we decode brain states from patients while they're performing memory tasks. We can tell when somebody is not encoding effectively, and we selectively stimulate the brain at the right time and at the right location to change the brain’s state. Essentially, our technology keeps someone in the zone of good memory performance.

Currently, we're applying this technology to patients with traumatic brain injuries with memory loss. It's not largely known that memory loss is one of the primary residual symptoms of traumatic brain injury. Even after someone has regained the ability to walk and talk after a brain injury, they're often left with debilitating memory loss.

One patient described it to me, saying, "It's humiliating. Imagine you're an editor, and during a conversation with a client about a project, you suddenly can't remember what you’re talking about." That's what it's like to live with memory loss.

There are no good treatments available for these patients today, and we hope to be the first. They're profoundly affected, with millions of such patients in the United States alone, and we believe we have a solution that can drastically improve their quality of life. And of course, this is just the beginning.

If it works for patients with memory loss due to traumatic brain injury, we believe we can translate this into other neurodegenerative conditions as well, such as mild cognitive impairment and even Alzheimer's."

If we dig into the technology side of things in a little more detail, I assume there is some form of implantable element?

"That's right. It includes an implantable component that's very similar to deep brain stimulators for Parkinson's disease. Additionally, there's a wearable component that resembles a cochlear implant earpiece.

In terms of form factor, patients will wear a part of the system with the battery pack positioned behind the ear. It's wirelessly powered, and the implantable component interfaces with the earpiece, which also acts as a communications hub.

This hub securely connects our device to the cloud, where all the AI algorithms reside. These algorithms develop personalized therapy for each patient based on their own unique electrophysiology."

In terms of funding, you mentioned you guys had an initial grant. What has your approach been in terms of securing additional investment and, how much have you raised?

"We developed the core technology at the University of Pennsylvania with $24 million from DARPA. Towards the end of that project, I spun out from the university to co-found Nia Therapeutics. Over the past several years, we've been developing our commercial prototype to take through the clinical trials process. It's a class three medical device, so it requires significant investment.

We've found individual investors who align with our vision and are incredibly patient. This is not an overnight get-rich-quick scheme. In neurotech, in general, it's incredibly difficult to pull off. You need vision and patience. This is a long game we're playing, and we've found success.

While VCs are great and play their role in the ecosystem, they don't always have that long-term vision and patience to wait for returns. We've found success with individuals who resonate with our mission and what we're doing, and we've raised over $12 million in the past few years to develop the prototype that we're now bringing through animal trials and into the clinic."

What would you say has been the biggest challenge up to this point, and how have you solved it?

"There are so many challenges; it's hard to choose just one, but the biggest challenge that the team has faced was an engineering challenge back in 2023. The device did not perform as expected, and we were several years into the project. It seemed really dire.

We had initially outsourced hardware engineering to an engineering partner, which was my initial mistake. If I were to go back and do things again, I would have been much more careful about which elements to outsource and which to insource at the beginning.

Thankfully, I had already built up the hardware engineering team within the company and we picked things up very quickly. We spent 2023 re-architecting the system from the ground up. Then, toward the end of 2023, we did a preclinical study in sheep and the device performed flawlessly.

So, we're back on track again, thankfully. 2023 was a difficult year, but the team came through with flying colours, and we're well-positioned for 2024 and beyond. We now have a clear line of sight to our first clinical trial, which we hope to initiate next year."

What do you think are going to be the biggest opportunities in Neurotech over the next couple of years?

"Expansion into new indications is key. Parkinson's disease, essential tremor, epilepsy, cochlear implants for deafness, and spinal cord injury—these are the bread and butter for neurotech. They support a $6 billion global market right now. But if neurotechnology is really going to take off, we need to expand into new indications.

That's what I'm excited about. From paralysis to depression to memory loss, there are many new and emerging indications being brought forward into the clinic. Companies like Paradromics and Syncron are pursuing paralysis, Inner Cosmos and Motif are pursuing depression, and Nia Therapeutics is pursuing memory loss — these are the groundbreaking companies and technologies that promise to broaden the market, raise the tide, and lift all boats.

Getting into new indications requires combining the right science with the right team and sufficient funding to execute. Developing new indications is really hard. So, getting the science right, getting the team right, and getting sufficient funding to execute is critical."

Now that you are 6 years down the Neuro startup road, what advice would you give to anyone at the start of this journey?

"This is such a hard question, and often because the challenges each company faces can appear unique, and often they are. But the general advice that I have is to surround yourself with the right people, especially the right mentors—preferably people who have done this before you.

There are so many pitfalls in neurotechnology development that having people along the way from the very beginning who have done this before, who can help you avoid them, is really key. So, seek out those mentors who can give you good advice.

The second piece of advice is regarding your team, your core team for the company. You've got to have the right people in the right seats. One person cannot do it all. It takes a village, so to speak. It's really important that the right people are doing things that are within their capacity and that they love. Even if you have the right person, but they're doing the wrong thing, that can be problematic. So, the right people in the right seats. It's trivial to say, but much harder to implement because it's not always obvious when you're making these decisions.

Finally, be persistent. There is no get-rich-quick scheme here. This is a long game. You have to have the passion, motivation, and belief that you can actually make a difference and be willing to stick it out through the incredible ups and downs that you'll inevitably face. So, persistence is key. And surrounding yourself with the right people and the right team can go a long way in helping you to be persistent as well."

I really enjoyed the chat with Dan. They are innovating targeting memory loss which impacts millions of lives and there are currently limited options for patients. Success in this space could be huge. The next year or two will be crucial for their progress and I'm excited to see how they develop.

If you like the article, feel free to follow and connect with me. We have some very interesting conversations coming up 😀