Changing the Game of Parkinson’s Disease: An Interview with Howard Federoff, CMO of Kenai Therapeutics

In the realm of neurodegenerative disease research, few challenges are as pressing as Parkinson’s disease. At the forefront of this battle is Dr. Howard Federoff, Chief Medical Officer and Scientific Co-Founder of Kenai Therapeutics. Bolstered by a recent $82 million Series A financing, Kenai Therapeutics is spearheading innovative efforts to develop new therapies for this devastating condition. In this interview, Dr. Federoff shares insights into the innovative approaches his team is taking to tackle this challenging disease and his aspirations for changing the game of Parkinson’s.

Howard, congratulations on Kenai’s $82M series A financing. Can you tell us about the company’s mission?

Howard Federoff: Thank you for having me. Kenai was founded just over two years ago with the focus on Parkinson's disease, particularly on the motor deficits caused by the loss of dopamine neurons. These neurons, which project from the midbrain to the striatum, are crucial, and their loss leads to symptoms like tremors and difficulties in daily activities as the disease progresses.

Our technology is an allogeneic iPSC dopaminergic product, which can be frozen post-manufacture and shipped globally. We've designed a clinical program that allows us to operate on patients within an MRI, enabling us to see the cells being implanted into the brain in real time. Our primary goal is to rebuild the lost motor circuits in the brain.

Next year, our focus will be on establishing the safety and tolerability of this approach. We're aiming to provide substantial clinical and neuroimaging evidence that we are indeed rebuilding these circuits. This could potentially roll back the disease state to an earlier stage, possibly reducing or even eliminating the need for current medications in some patients. And we believe that this will further lay the groundwork for the work that we want to do subsequently, which is to refine this product to cover the broader Parkinson's spectrum, including early onset and more severe cases, areas that no other company is currently targeting.

This is a very bold vision and approach.

Howard Federoff: Yes. We're going to be doing something that could scale to meet the global Parkinson's need given the cryo-preservation, the ability to ship, thaw, and deliver. We've developed a neurosurgical approach that I think will be very safe and well tolerated. And most importantly, as we begin to move through from our first cellular product down to some of our edited products, we'll be able to take on a substantial and increasingly greater percentage of all Parkinson's patients, including those that have younger onset, milder disease, and those that have more severe disease. So, in a word, we're excited that this was potentially a game changer.

What challenges do you foresee, and how do you plan to address them?

Howard Federoff: This is actually the fourth Parkinson's company I've started. My belief is that as technology advances, we can move beyond just stabilizing the disease, which is the focus of many gene therapies, including one I co-founded. We're now aiming to rebuild the brain circuits that are affected. So far, the focus has been on motor dysfunction, but our next big challenge is addressing cognitive impairment and dementia, which not all Parkinson's patients develop but is a significant issue. Our pipeline is designed to first establish safety and efficacy in motor restoration. After that, we'll focus on preventing or delaying cognitive decline, a major unmet need in Parkinson's that most companies aren't yet tackling.

So how important is imaging in your clinical trials?

Howard Federoff: That's a fantastic question. Imaging is crucial to our trials. We're the only company, as far as I know, that uses not just standard imaging techniques to track dopamine production in the brain, but also a cutting-edge method developed by neurologist and neuroimaging expert David Eidelberg. This technique involves a special tracer that highlights areas of glucose metabolism, which is particularly relevant because Parkinson's disease affects this process in the brain. Eidelberg's work suggests that as we form new neural circuits, we can actually see them developing in real time through this advanced imaging. So, not only can we track dopamine production, but we can also visualize the rebuilding of brain circuits as it happens, which we expect to correlate with clinical improvements. So yes, imaging is incredibly important to our work.

Looking at neuroscience as a field broadly, it is often regarded as the Holy Grail. What are your aspirations for Parkinson's?

Howard Federoff: The biggest challenge I think that the entire field is now grappling with is how to develop therapeutic approaches that actually are restorative, that can rebuild some of the lost infrastructure that accounts for the clinical presentation. Separately, we need to take on the non-motor features of Parkinson's disease, which include cognitive decline and dementia, among others.

I think the science is continuing to advance, and there will be even more sophisticated science underpinning the way we think about therapeutics development in Parkinson's. It would not surprise me that within the next several years, with the advent of better and more on-target ability to edit in vivo, we will see other approaches emerging, whether they are to be conveyed by a gene therapy approach, a combined cell and gene therapy approach, or a nano-lipid particle and cell approach. This should represent an enormous amount of hope.

I'm staying focused on what I think Kenai is going to be able to do and to bring it into the clinic in a meaningful way, and hopefully a robust clinically beneficial way. But we have a lot of aspiration to go even beyond that. One aspect that we haven't touched on is the chronic neuroinflammation that attends all of Parkinson's disease, as well as other neurodegenerative disease. And I have a strategy that we've outlined that will be a later generational product to take that on as well. So the future is, I think, going to be laden with lots of interesting approaches, and I hope ours is just one of many.

What excites you most at Kenai?

Howard Federoff: Earlier today, I spoke to a Parkinson's patient in Toronto who is so enthusiastic to be involved. And although he may not be at a clinical stage where a transplant could be contemplated, his enthusiasm level for being able to, if you will, get the word out and talk about this among the broader Parkinson's community is very reassuring to me because it tells us at the least that I think we're on the right path. This excites me. And I hope we can accelerate our progress on that path and really make the difference that I've often wanted to believe companies such as ourselves can make.