Treating Neurodegenerative Diseases with Rob Etherington, CEO of Clene Nanomedicine

Listen in on our conversation with Rob Etherington, CEO of Clene Nanomedicine, a company pioneering nanotherapeutics for neurodegenerative diseases like ALS, multiple sclerosis, and Parkinson's.

Rob discusses Clene's unique approach to improve mitochondrial function through a novel nanotherapeutic called CNM-au8, which has shown promising outcomes in clinical trials. He highlights the challenges in drug development, including funding and FDA approval processes, and underscores the importance of resilience, continuous learning, and strategic partnerships in advancing biotech innovations. The episode also touches on Rob's personal philosophy on leadership and the importance of women in leadership roles.

https://clene.com/
https://www.linkedin.com/in/rob-etherington-431718/ 

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Music by keldez

Transcript

0:01

Hi there! Welcome to the From Lab to Launch podcast by Qualio, where we share inspiring stories from the people on the front lines of life sciences. Tune in and leave inspired to bring your life saving products to the world.

Meg Sinclair: 0:17

Greetings, everyone. Thank you for tuning in to the from lab to launch podcast brought to you by Qualio. I'm Meg, your host, and I'm delighted to be here with you today. Before we dive into today's episode, we'd love it if you could take a moment to rate and share the podcast with your circle of science enthusiasts. And if you're interested in being a guest on the show. Please check out the application in the show notes. Today we're excited to welcome Rob Etherington on the show today. Rob is the CEO of clean a trailblazer in the field of nanotherapeutics for neuro neurodegenerative diseases, such as ALS, multiple sclerosis and Parkinson's. Rob has over 30 years of sales, marketing, and leadership experience in biotech, and as founding CEO of Clene has helped raise over 250 million in funding. And under his leadership, Clene has completed multiple phase two studies and long term open label extension studies. For now, let's jump in and get started. As someone who has had a loved one affected by LS. I'd love to hear more about this amazing nanotechnology being developed and how it can improve patient outcomes. So I'm really happy to welcome you today to lab to launch Rob.

Rob Etherington: 1:29

Thanks, Meg. It's a pleasure to be here. And sorry about that news, which I didn't know before you just said it about your loved one with ALS, a devastating disease. Uh, let me explain a little bit of context for your listeners about kind of what we're doing and how we're doing it. The human nervous system is complex and highly metabolically active. Uh, just putting that into context, our brain is about two to 5 percent of our body weight, depending upon who we are, but it is responsible, frankly, for About 25 percent of my energy utilization every day, day and night, uh, 20 percent of my oxygen consumption, 20 to 25 percent of my glue glucose utilization. So it's highly, you know, highly, highly metabolically active and the neurons themselves depend upon the mitochondria for all of the energy. that they require to do what you and I take for granted to move and walk and to talk and eat and to chew and breathe. All of these things that you and I just do and have been doing since childhood. But in neurodegenerative diseases, including ALS, these essential aspects of life that we count on start to be taken away. And why that happens is because these mitochondria that produce energy, there's a number of processes going on that underpin that neurotransmission and these neurotransmission signal as I just said, how we eat and talk and move and walk and think and breathe. And so what clean is doing is something totally unique and novel. Uh, we've taken, I'm holding it up here in my hand, your listeners only can't see it, uh, you've, your viewers can. This is a 60 mil suspension of our nanotherapeutic, we call cinema you eight. Uh, patients drink this every morning in the clinical studies that we're organizing. Uh, if I was to be blindfolded, uh, and to drink a glass of room temperature water, or cinema, you wait, I would not be able to tell the difference. In fact, our asset. Uh, what we do for placebo in all of our clinical studies is, is literally purple colored water. Sinemauate, because of the gold nanotherapeutic in it, uh, reads as purple to the eye. And why this is so relevant is because the World Health Organization predicts that, uh, these neurodegenerative diseases of which I speak, not just ALS, but MS, multiple sclerosis, Parkinson's, and I can go on, there's a lot of them. They will become the second most prevalent cause of death in the next 20 years. And so it's pretty obvious that a therapeutic breakthrough is urgently needed. Uh, and, and what we're doing with our asset is pioneering catalytic nanotherapeutics to treat these diseases. And what I mean by that is we really target the improvement of the mitochondrial function, and we do that via the catalytic active of our asset to improve nicotinamide, iodine, and dinucleotide to reduce reactive oxygen species, which are to, um, a byproduct of energy production and an essential energy metabolite and taken together. This is really pioneering a new way to restore and to protect the way the neurons work.

Meg Sinclair: 4:41

A first of its kind. Pioneers.

Rob Etherington: 4:43

Yeah, it is. It's actually important to, to highlight that for a second. So most drug development is small molecule chemistry. That's how it was for basically a hundred years nearly. Then in the last, uh, number of decades, biologics have taken also their Their progress aside, small molecule clean is doing neither of these, uh, what we're doing is intersecting physics and material science, basically a therapeutic elemental metal at physics scale. So we're talking atomic scale. We're talking nano scale. We're talking small enough to cross the blood brain barrier scale. And we're doing that to drive energy into the neuron.

Meg Sinclair: 5:26

Amazing technology. Amazing. So, um, what are some of the current and potential applications, um, for all of these vast, uh, uh, neurodegenerative, neurodegenerative diseases?

Rob Etherington: 5:39

Well, the, the good question, the hallmarks of neuronal death converge on mitodysfunction and these nicotinamide adenine dinucleotide pathway deficits that I, I mentioned earlier. And there's a whole series of, um, pathogenic insults that kind of converge. to cause the stress on the neuron. And the result of that is mitodysfunction. And, uh, again, as I mentioned, a whole bunch of other things. So what we're doing is we're, we're focused on ALS first amyotrophic lateral sclerosis, um, uh, sometimes called Lou Gehrig's disease after the famous baseball player who, contracted this disease and went quite public with it in the 1930s. Unfortunately, it took 60 years for the very first drug to be, uh, approved by the U. S. FDA. That drug, now called Rileazol, is a generic. It was approved in the mid 90s and is available mostly around, pretty much everywhere around the world. But there's been, despite a lot of science, a lot of money and a lot of attention, very few other true breakthroughs. And there's been a lot of, um, consternation about this, including in the last few months with, uh, um, the failure of some major phase three studies. But so we started at ALS. We also, um, have a multiple sclerosis project underway, uh, because our same asset can be used in MS. And we've also concluded one Parkinson's program, And that is just the beginning. We think there's the opportunity. For a number of these, uh, neurodegenerative diseases, uh, to be attacked, um, uh, or to be really helped. That is probably more precisely said by CNMA.

Meg Sinclair: 7:23

Terrific. Well, we'll have to stay tuned on what, what else comes down the pipeline for clean. So far, what are the most significant challenges you face in developing new therapies for these neurodegenerative diseases and how have you overcome them?

Rob Etherington: 7:37

First, the challenge always is funding, finding enough money to do something completely new. I'm fond of a statement that the famed author Stephen Covey said, that there's never a breakthrough without a break with, and he means break with convention. So we had to, you know, really help others understand what a clean surface nanotherapeutic suspension is, uh, and I say clean surfaced because we use no synthetic chemistry in our process, none, we had to pioneer and create this process. process ourselves. It was organic to clean. Uh, the founder Mark Mortenson and chief science officer is the one who came up with this. I still work alongside Mark today. And Mark had the idea, um, some time ago actually, uh, to figure out how to shave Adam's Of of therapeutic metals often and self aggregate them in a water suspension so that they could be taken by mouth orally. And he did this with 150 present to date and counting patents that he applied for and received. And then we've also done a number of trade secrets. So, so, so first funding to answer the question we had to start, uh, Helping others capture this vision of what this could be. The second thing we had to do is help the U. S. Food and Drug Administration, which has been our primary focus as a United States based company, understand the safety aspects of this. We theorized from the beginning that, uh, clean surfaced, uh, nanotherapeutic Atomic scale, 13 nanometers in size. That is remarkably small. Um, so small that again, there can be a crossing of the blood brain barrier, which is difficult to achieve and we theorize that we would have clean toxicity and that is indeed been the case. We're grateful for that. But that took many years for us to help persuade the FDA about that. We had to do. Work in, um, mice and, and rat and mini pig and dog and then to human phase one work. And that took many years and a lot of cash to basically Compile a compelling safety database and gratefully, you know, knock on collective wood here. We have now over 600 years of collective subject exposure across the ALS, MS and Parkinson's landscape of our disease clinical studies without identified safety signals. What that means is we have not a single serious adverse event related to CMAU8 that's been considered severe or life threatening or resulted in death. And our drug is remarkably safe. Um, has a remarkably high tolerability, meaning, uh, if patients can drink, uh, a glass of water or put that water if they have ls and they've lost the ability to drink into their feeding tube, then they can take our asset without very many side effects. Uh, just to inform your listeners, sometimes we see some adverse events that are transient or mild, such as a headache or GI, but patients don't complain about these on balance. And we're, we are routinely told by the clinicians that are involved in our clinical studies that our drug is amongst the easiest to take. So there's two things that we had to sort through, it took many years, cash to get this new novel concept up and running, um, safety. to prove so that we could, um, have the US FDA let us proceed into phase two clinical studies. Uh, then we had to identify and develop our targets, um, how we would tackle the diseases and what clinical endpoints we would use. And that has not been smooth. It never is in clinical drug development. Uh, we've missed some primary endpoints and yet we've seen other things occur that we didn't expect that now have completely pivoted our focus, namely survival benefits that we saw in ALS. Now we've seen it across three completely different types of patient programs, but we didn't expect we'd see that survival at the beginning. We thought we'd see more classically functional change. Um, but the reality of what we're doing is it takes, um, Some time for our director to study state. So on short studies, we don't see functional change as much, but we do see survival. And so that was another. learning. And then a fourth is how to reliably manufacture this to get to scale. Um, that's always a challenge with a new drug, uh, how to, um, be able to, uh, achieve what is called the CMC aspects of drug development, chemistry, manufacturing, and controls so that the FDA is satisfied, uh, that what we do is. Reliable and, um, yeah, that's good. Replicability. Uh, in other words, we do the same thing every time. The asset, uh, is always the same for patients to drink.

Meg Sinclair: 12:24

Well, that kind of leads me into my next question. I am a quality professional myself, and given that we do quality management systems here at Qualio with the complexities and high stakes of. What you've been developing and on the front lines of innovation with the FDA, what strategies have you used as the CEO to maintain and improve quality as you've been going from the lab to market distribution?

Rob Etherington: 12:49

Um, so we're, we're not a market distribution, of course, yet we don't have an approved drug, but we're, we're, we're preparing for that. Um, so that has been, you know, that, that, that. 80 percent of the people at clean have been involved in that process, either manufacturing S. O. P. S. Standard operating procedures, uh, regulatory C. M. C. requirements. Um, and in all of that, about 80 percent of our team has been completely focused on that piece because, uh, that was A big piece of oversight that the agency wanted to, um, be certain of all of our early meetings with them were all about how we could make certain we had the quality and we could replicate, uh, this and, uh, that sometimes is tedious, um, work. Uh, it's, it's a lot of paperwork. It's a lot of T crossing and I dotting. And then also, since we were pioneering this from scratch, we had to figure out how to build it from the ground up. Was one aspect to develop our active pharmaceutical ingredient, but then to move that to scale and to human dose and to sufficient concentration was a whole bunch of other work. That's actually one of the reasons why we have chosen not to do any manufacturing with a contract manufacturing organization. It's just so complicated that we wanted to, in our case, we wanted to have, um, it under our, uh, our purview and within, uh, you know, our responsibility entirely. But also we wanted to keep secret what we do with a series of trade secrets so that, uh, somebody couldn't just go replicate it, um, you know, outside the door. So that, that, what that enables us to do is we have our patent, um, But we also have, uh, the ability, we think, to, uh, keep trade secrets and, uh, make it very difficult for somebody even post patent expiry to come behind us.

Meg Sinclair: 14:45

Very strategic, um, in your, uh, Roll there. Um, so now I'm curious. You've helped raise a significant amount of capital for clean to be able to accomplish all these milestones. What has been challenging for you, especially in the current economy? Um, and what advice would you give for people trying to raise capital?

Rob Etherington: 15:08

Yeah, since 21 when, uh, you know, we kind of peaked in biotech 22 even still 4. has been remarkably complicated for pre revenue biotech companies. Um, uh, we have the good fortune, which many of my peer base does not, that we still trade above our enterprise value, which to say our, our cash, um, on hand and the length of cash we have money for, um, our market cap is still above that number. So many companies in the neurodegenerative space and elsewhere have struggled, struggled, struggled to, We're going to raise the capital, uh, since there's been this flight out of biotech in the last, um, two and a half years, but I, I sense it changing. Uh, we, since J. P. Morgan in January of this year, uh, I think there's been, um, uh, continued, uh, refocusing and investment beginning back in the space, uh, still companies that are a dream or a thesis as opposed to a clear path to commercialization, uh, still are struggling and that would include clean, um, which is the reason why, you know, we're working hard to see if we can get all of our solving Data together to consider the possibility of accelerated approval of the agency. We had a meeting with them last year and They gave us marching orders and we're, um, uh, seeing if we can accommodate a number of questions they had to get back on track for a new drug application. But also too, we're preparing now for two phase three studies. We have a phase three ready asset that has been completely de Been de risked safety wise and is ready to go. Uh, and so, um, that brings me to, uh, what do we also do? Well, one leans into partnering. Um, there's, there's been a dearth of, uh, good assets in many of the big pharma pipelines or even medium and small pharma. And so small, innovative biotechs like clean, uh, and you know, we, we enable the opportunity to, uh, bring something completely outside the box that could be. Markedly complimentary to, um, you know, the drugs in, in, in these pipelines. And we have a number of pharma companies now looking at clean, considering exactly that idea.

Meg Sinclair: 17:17

Can you tell us anything more about those partnerships or collaborations are still too early to share?

Rob Etherington: 17:22

No, too early. Uh, and anything publicly, uh, but we have said that, uh, we are open to partnering. We have welcomed, uh, other pharma companies to come under the hood under a confidential disclosure agreement and look, really look at our data. And, uh, we're doing this in two ways, uh, ALS and MS. Uh, we've not spoken much about MS or ALS clinical data yet, um, but in both cases, we have something very novel and unique that the marketplace, uh, we believe definitely requires for either the ALS or the MS patient.

Meg Sinclair: 17:56

They sure need, um, all the treatments and support they can get, um, to improve their outcomes. So it's terrific. And I love that creating an ecosystem of partnerships and collaboration to really move the needle for patients. So terrific. For our aspiring scientists and innovators listening to the podcast, what advice would you give those looking to make a significant impact in nanotechnology or just biotech at large?

Rob Etherington: 18:23

Well, uh, there's infinite number of roadblocks and hurdles that one either has to push through or jump over, push through the roadblock and jump over the hurdle. And so there's a resilience, um, that is obviously requisite with this work. Um, uh, so that, that's one thing, uh, is to just keep pressing forward. If your science is solid. And if you're seeing progress, then to count all the victories and push through the defeats. And again, clean clean has had to figure out a number of these things. We had to make sure we had. Um, a stable asset that had room temperature stability. That took a lot of work. Uh, we've had to pivot, uh, from, uh, clinical endpoints that we didn't meet into clinical endpoints that we did, and then build new clinical studies off of these we've had to understand biomarker paths, uh, that, uh, are, are very relevant in our respective spaces that, uh, You know, one biomarker in particular, that's kind of a very critical biomarker and, uh, ALS called neurofilament light, uh, as the neuron is attacked, it kind of leaves, uh, this said kind of colloquially, a debris field in the serum and the plasma of the blood and I can measure it. And, uh, if that neuron is under extraordinary attack, then that neurofilament, um, light, and it's not light like sunlight, but rather light, like molecular weight, uh, it can be measured. And we. High levels of neural filament light in the serum is indicative of a massive attack on the neuron, which is exactly what happens in ALS disease. So I frankly had never heard of neural filament light when we started clean and now we talk about it all the time and we explore it exhaustively. So that's another example is one has to be in constant learning mode of of our respective spaces to make progress. So, so resilience. Uh, constant learning and figuring out how to, to solve the infinite number of problems that develop along the path.

Meg Sinclair: 20:18

Infinite number of problems. No big hurdles, no problems. That's great advice though. Um, so switching the gears a little bit, we saw in your bio that you have seven daughters. Can you tell us a little bit about your personal philosophy when it comes to leadership, especially women in leadership, which we hear a lot about these days.

Rob Etherington: 20:39

Good question. The first I've ever been asked that one. Um, seven daughters. Indeed. uh, the last two are now in college. The other five are all either concluded. I have one daughter that has a special needs as well. That didn't go to college, but is actually, um, nonetheless, uh, an assistant manager, at her office and, uh, despite no college degree, uh, shows up, does the work and leads her peers and, uh, she can be counted upon expressly to, uh, despite her special needs. And so I think that is just one, you know, one example. Um, uh, but women in leadership are critical. Uh, I actually have had, uh, strong women who do amazing work, uh, alongside me at, uh, at. Pfizer, uh, where I was first at nine years. At Octillion, where I was for 13 and then here at clean for 11. Um, and, uh, I've, I've worked for women. Uh, I find most of my key opinion leaders actually are female physicians. In fact, Um, I was just with the top doctor in Canada last night, um, returned back from Montreal this morning. Um, she's an extraordinary woman who has done tremendous progress. And the number one a LS doc in the country by most people's argument is merit. Sovich, also a woman. So I, I love, um, actually the insight that, that women bring and that, uh, women lead out. And as a dad of only girls, seven of them as I, as you noted. Um, it's, it's been fun to watch them thrive and lead and learn and make their place in the world. And it's critical that we, uh, as Sheryl Sandberg says, uh, lean in to female leadership.

Meg Sinclair: 22:26

That's terrific. And you're in good company. My dad was a, it was a dad of four daughters. So, um, I'm sure he, he can relate there. So, and I think he brought up some strong women as well. So,

Rob Etherington: 22:39

um, our last special, any dad that specializes in girls is a true dad. Yeah.

Meg Sinclair: 22:46

Yeah. True Dad. I like that real badge of, of honor there for dads. Um, our last question to close this out is a bit of a fun one, though. I already got you with a surprise question there with the daughters. We love to ask each of our guests, if we ran into you at a bookstore at a Barnes and Noble, um, the library, what section would we find you in?

Rob Etherington: 23:05

I love historical biographies. Um, love them, um, and all different types. Uh, uh, one of my passions is actually working in my yard. Um, I spend a ton of time in the yard, uh, gardening, um, raising flowers, uh, et cetera. I like to be out in nature. And while I'm there, I listened to a lot of podcasts or when I'm on planes, I listened to, um, I would rather I read, uh, historical biographies. So, uh, and again, wide ranging. I just finished the Elon Musk book. I'm presently, um, listening to the Barbra Streisand book and on the plane just this morning, I was learning about the history of food in the White House from George Washington, all the way to the present era and the importance of state dinners. So, as you can see, that's a very wide, um, slice, uh, but, uh, in any, any historical biography, Um, thrills me, uh, whether it's Churchill or, uh, or Hamilton or Benjamin Franklin or I can go on and on.

Meg Sinclair: 24:04

All right. Well, you're in good company there as well. I'm a big historical fan having read, uh, Catherine the Great and Hedy Lamarr's biographies recently. So, um, yeah. History is always a fun one. Well, thanks Rob so much for joining us. It was really exciting to hear about all of your work with Clene and all the work you're doing for patients with ALS, MS, and Parkinson's, and hopefully more.

Rob Etherington: 24:28

Thank you, Meg. If we're right with this thesis, we think we're seeing a survival benefit for ALS that's desperately needed that patients are able to live longer. And if we're right with this thesis in multiple sclerosis, we believe that we are seeing data that is improving vision and cognition on top of standard of care DMT. And that's never happened either. So, in both cases, a survival benefit and an ALS and a functional benefit of vision and cognition improvement in MS would be a major breakthrough. And we're thankful for all the Investors and patients that, um, and clinicians that, uh, work together with Clene on this potential mission to develop a gold nanocrystal suspension as the very first cellular energetic catalyst. And we're grateful for how they help us do this. And we're grateful for the opportunity to talk with you, Meg, about it today.

Meg Sinclair: 25:18

Well, thank you, Rob. It was a pleasure. Please check out the show notes to get more details about Rob and Clene. Thanks so much.

25:29

Thank you for listening to this week's episode of From Lab to Launch, brought to you by Qualio. If you like what you've heard, please subscribe and give the show a positive review. It really helps us out. For more information about Qualio, our guest today, or to be a guest on a future episode, please refer to the show notes. Until next time.