Rich McCormick: Hi, I’m Rich McCormick, executive vice president of CRO operations here at Vial. Today I have the pleasure of welcoming CEO of Clene Inc., Rob Etherington to our First In Human podcast. Rob, thanks for joining us. Would you mind giving us a brief intro?
Rob Etherington: Thanks for inviting me rich. It’s a pleasure to be here. I’ve spent, I guess it’s now nearly 32 years in pharmaceutical drug development and all different stripes. From grad school I went straight to Pfizer where I spent 9 years. Culminating at the end of that period as 1 of the team leaders for the Lipitor franchise. So I had an opportunity to work with a drug near and dear to many people’s hearts because it’s certainly 1 of the most prescribed medicines ever.
And then I joined a small biotech company in the year that we took that company public Actelion that hopefully none of your listeners have heard of are very few in any event. Because Actelion focused on a rare orphan disease called pulmonary hypertension. Because of our success in that space we became the largest biotech in Europe and subsequently sold itself to Johnson and Johnson.
I spent 13 years there as the chief commercial officer in a variety of roles between Basel, Switzerland, and primarily the San Francisco area, and then founded in the Bay area Clene. Which is a nanotherapeutic company, we’ll be talking about what nano means in a minute. I’ve been here now for 11 years beginning in April.
So 10 years, almost 11 as we speak.
Rich McCormick: Awesome. Thanks Rob, that’s a good segue to jump right in. So what inspired you to venture into the field of nanotechnology? Maybe tell us a little bit about it as well. And also, you know, what inspired you to start Clene?
Rob Etherington: So I joined the work of our founder scientist, Mark Mortenson, who is a physicist by trade, as well as a material scientist.
And he came up with this very clever notion, and I’m holding it here in my hand. Your readers probably can’t see it, but this is a 60ml bottle, which is about a quarter cup of a nanotherapeutic suspension that patients drink orally every morning. And just to give some background, for decades in some areas here in Western medicine, but dating back centuries in Eastern medicine, the idea of a therapeutic elemental metal and it having some medicinal efficacy has been well understood.
Indeed. Your grandmother and mine in the west. If she would have had rheumatoid arthritis, she would have had gold salts injected into her joints to help her with her rheumatoid arthritis. And so we had the idea, “I wonder if we could take the mechanism of a nanotherapeutic, shrink it super small” 13 nanometers in fact.
So just to give that some perspective. We’re talking at you know, the level of atoms and the ability to drive energy into the failing mitochondria that powers your and my brain. We had the idea, what if we could do that with a catalytically active nanotherapeutic the patients drink and that is exactly what we did do.
We’ve been. Working in this space now for 11 years, our particular focus is neurodegenerative diseases where the central nervous system, the brain, the neurons that drive the electrical activity that you and I rely upon for our cognitive function, but frankly, equally relevant for all of our movement, the way we move and walk and talk and chew and even breathe.
That is a extraordinarily beautiful choreography of electrical signals that our neurons are driving back and forth in our brain and in our central nervous system and to the muscles of our arms and hands and legs and lungs and what our asset is doing is improving the mitochondria and its ability to drive function in these key elements that you and I rely upon for that movement and function.
And our particular focus is ALS multiple sclerosis.
Rich McCormick: That’s really [00:05:00] interesting. So what are some of the current and potential applications, you know, of combining physics, material science into quantum nanomedicine with the potential for vast applications in these neurodegenerative diseases?
Rob Etherington: Well, we first completed some translational medicine work, whereby we were able to show that our drug taken by mouth orally got into the stomach into the bloodstream across the blood brain barrier and drove the key bio energetic metabolites that you and I rely upon for energy. This was done using a very sophisticated technique called 31 phosphorus magnetic resonance spectroscopy.
And that’s a lot of words there. But basically, what we did is used a very high powered MRI machine to image and to see the energetic capacity of the brain change. And we were able to reverse the clock by decades. In what would be normally construed as healthy aging, but reverse the clock in patients that were either Parkinson patients or multiple sclerosis patients.
And so we showed therefore that a brain, yours and mine in my brain is only about three to five percent of our body weight, but it’s consuming about a quarter of our daily energy every day. A huge energy sink that’s required a fair amount of brain power to drive the energy that you and I need.
And so that was proven to show an improvement in the 2 energetic metabolites that are critical ATP and nicotinamide adenine dinucleotide which are again these 2 energy metabolites that our brain uses for let’s call it the gas that drives our function. Then what we did is proceeded into two ALS studies and one multiple sclerosis study, all of which have concluded in the last 18 months and have shown our ability to improve function, improve the way again, as I noted earlier the way patients move and walk and talk and eat and chew and breathe.
Rich McCormick: So, how does your company’s approach differentiate itself from traditional treatments? What are potential advantages, what does it offer in terms of patient outcomes?
Rob Etherington: So what our asset is, patients can drink it orally, first of all. And that is a big advantage because so often in the central nervous system diseases of which I’m speaking, these neurodegenerative diseases like MS and ALS patients may have sometimes a struggle to take the medicine.
It depends on what medicine we’re talking about, but some are infused. Some actually have to be injected. Others are oral pills. Recipes of chemistry. Ours is an oral suspension that if you can drink a glass of water, you can effectively take our medicine. And what the big advance though, is the mechanism by which it works.
And so we theorized from the very beginning that we would be able to do this with clean toxicity. That is to say, with a strong safety profile. And that has indeed been the case. Our drug assets. Across either ALS or MS have not a single serious adverse event that has been related to the drug. Not a single one.
And that is a massive advantage in the field because it means that our drug can also be taken on top of standard of care, which is to say, whatever therapy the doctor is otherwise prescribed, we tell the physician to take that drug and to continue to administer it, place our drug on top, because what our drug is doing is something
very different. So it’s important, I think, for your listeners to step back and add a bit of context here. The World Health Organization predicts that neurodegenerative disease will become the second most prevalent cause of death within the next 20 years. And so it’s, I think, pretty obvious that a therapeutic breakthrough is urgently needed.
Medicine, modern medicine, has solved a number of issues, but many still remain, and that includes neurodegenerative diseases. And by these, This is where impaired mitochondrial activity and compromised cellular metabolism lead to the death of the neuron. And so what’s very unique about our approach is we’re pioneering a catalytic nanotherapeutic that can be taken orally by mouth.
And again, if a patient can drink a glass of water or can administer such liquid in their feeding tube, which is the case, very sadly, many times in the disease of ALS, they’ve lost their ability to process liquid down their throat and in their mouth down into their stomach and so a feeding tube may be necessary. But even in that instance, if they can administer liquid, which is, you know, all of us rely upon liquid for life, then they can drink our medicine. It has no taste. If I was blindfolded, it would taste effectively like water. And what we’re doing is targeting the improvement of mitochondrial function.
As I mentioned earlier, this is indeed pioneering a new way to restore and to protect neuron function.
Rich McCormick: It’s really interesting, so the drug you’re referring to your drug CNM-Au8. These are different disease types. Well, they’re all neurodegenerative, but you’re [00:10:00] mentioning different diseases is the approach the
same?
Rob Etherington: Yeah, that’s a very unique thing. Yes, it is indeed. So that is unusual for our approach, that most times you know, what, what might work in MS, multiple sclerosis does not at all work in Parkinson’s or ALS, but the core issue that we’re addressing has the ability foundationally to mean that our drug could be applied to
all three of these diseases and the reason why is because these neurodegenerative diseases all involve neuronal death and the hallmarks of how the neuron dies, and again, the neurons are effectively all of the ways that our nerves talk to each other to enable us to move and walk and talk and eat and chew and breathe and think.
There’s a series of insults that converge to cause that neuron to die. But what our asset is doing is enabling mitochondrial dysfunction to become mitochondrial function again. And our drug is enabling energetic pathway death of deficit to actually become resolved. So effectively what’s happening is we are improving mitochondrial function.
We’re improving the neuron’s survival. And the way the neuron functions by the administration of this oral medicine called CNM-Au8.
Rich McCormick: So, I’m sure this was not as easy as you’re making it sound. There had to have been challenges along the way. Can you maybe walk us through some of those challenges that you faced in developing nanotechnology based therapies?
Rob Etherington: Yes, it’s indeed not easy. Anything once discovered sounds easy, but this is now in my case, 11 years of work and in Mark Mortensen’s case, more than 20. So the idea of how to shrink a series of atoms of gold and to hold them together in a crystal structure that has medicinal efficacy and to do it in a suspension that a patient can drink orally has now required more than 150 patents that have been prosecuted worldwide.
A number of trade secrets that we’ve chosen purposely not to patent and Clene manufacturers, which is unusual for a small biopharma company like ourselves, manufactures our own drug entirely by ourselves and we do that so that we could keep the trade secrets and the methods by which we do this quite proprietary.
Now it took the FDA a while to get their head around the world’s first nanotherapeutic that would be used in neurodegenerative disease and to understand how our drug was used safely. So they put us through the paces with a series of animal studies and then a pretty comprehensive series of what are called phase one human safety studies to illustrate and to prove definitively that our drug was safe in these clinical programs and in the animal work, but that was all checked off.
In fact now 11 years in, there is no longer a concern raised at the safety side of this because we have some side effects. We have a headache that occasionally occurs. We have some GI disturbance that occasionally occurs, namely nausea, occasional diarrhea. But on balance, these patients all are talking about these as what are called mild to moderate side effects.
And they’re not unmanageable. In fact, we do not have drug discontinuations because of the side effects on balance. And we do not have drug interactions, what are so called drug interactions. So we’ve now resolved the safety side. The challenges still occur with respect to showing a completely the clinical benefit.
We thought that we would see function as 1st indicated primary end points, and in fact, what we ended up seeing is clinical worsening changes and survival benefits. And that was not expected, what I mean by that is many ALS and MS studies. Well, let me focus on ALS first. Many ALS studies have been unsuccessful over many decades to improve survival.
And so the ALS field naturally moved to function change, the way patients are able to continue to move and walk, et cetera. And, our study was not designed of a sufficient duration now, in retrospect, to achieve a functional change on the primary endpoint. And we, in fact, missed the primary endpoint, but we were very surprised to see in the core Harvard study that was the largest of the 2 programs that our secondary endpoint of survival was met.
That is to say we saw that patients had a survival benefit with a 90 percent reduction of death at our 30 milligram dose at the 6 month period. And that data is, in fact, concordant or similar to what we saw in the rescue period because we saw there a 75 percent decreased risk of death as we continue to follow these patients and that data was [00:15:00] also seen in further end points that were considered secondary or exploratory in terms of reduction of clinical worsening.
That is whether or not a patient needed a tracheostomy to breathe, whether or not they needed a feeding tube in order to take their food and water, and whether or not they passed away or not. Clene had an advantage for drug versus placebo in an improvement of clinical worsening versus placebo patients.
Rich McCormick: So maybe shifting to the business side of things. Can you tell us about, you know, any significant collaborations or partnerships that Clene has engaged in, and how do you rely on those for, contributing to your success?
Rob Etherington: So, these clinical studies have been done in partnership with a number of academic centers of excellence that focus on these neurodegenerative diseases worldwide.
The multiple sclerosis project called Visionary was done with 9 multiple sclerosis centers of excellence in the country of Australia. And the Healy study was done with 57 of the most important ALS centers of excellence in North America primarily anchored from the Harvard Healy ALS program at Mass General Hospital in Boston, Massachusetts.
In addition to that, we have partnered with some of the leading academic labs in the country to help understand mechanistically how our drug is working. And this partnership between these academic key opinion leaders that focus on these neurodegenerative diseases globally and are leading the efforts in these sciences.
Initiatives with some of the best assets that have ever been proposed have been truly beneficial to Clene because we have been able to leverage their expertise to design these programs and figure out the next steps, including understanding the nature of the study and how to get the right end points designed.
I should also add that we just received in the fall. In a partnership with the United States Government’s, National Institutes of Health, a $45 million grant spread over four years to enable another compassionate use program for Clene. And I say another because we already have three compassionate use programs.
This one recently funded from the NIH for the 45 million I mentioned will be our fourth such compassionate use program. These are specifically called expanded access protocols. There are special protocols that the FDA allows for drugs and rare orphan diseases, such as ALS and when there is compassionate use that is arguable for a particular drug, which is the case with Clene safe as it is to be used to help patients in the ALS space.
Rich McCormick: It’s very admirable. Rob, what advice would you give to aspiring entrepreneurs looking to make an impact in the biotech space?
Rob Etherington: Well, anybody that comes into biotech comes in with some resiliency and certainly 1 needs a lot of this as we’ve already noted the timelines are long.
And as we’ve already noted, there’s risk of failure throughout and there’s a fair amount of capital that needs to be raised. We are grateful. In fact for the patients that have participated in all of our clinical initiatives. Without them, we could not have achieved anything. And we are thankful for the investors that have funded this important work and neurodegenerative diseases because without their capital, we could not have helped these patients.
Rich McCormick: Yeah, definitely. So, last question, looking ahead, how do you foresee Clene transforming
healthcare?
Rob Etherington: As we continue to develop this asset, and if we can take it to market, which is the goal this year, potentially to work with regulatory agencies to see if we can get a new drug application filed in the space of ALS if we’re able to improve the energetic capacity of the mitochondria and, central nervous system diseases.
If we’re able to improve survival in ALS and or function in multiple sclerosis on top of standard of care, it could be groundbreaking. Especially to do this with a safe asset. The patients drink every morning that tastes like water, and they’re drinking only a quarter cup to be able to drive energetic function.
With such an asset , then this could be groundbreaking and could really change the game for the way that ALS is treated, especially given that our drug is non competitive with other assets and can be taken in combination with other therapies. That the physician may prescribe.
Rich McCormick: Yeah, that’s great. So, Rob, it’s been a pleasure meeting with you today and really appreciate you being a guest on Vial’s First in Human podcast. The team here at Vial wishes you and your entire team at Clene Inc. Nothing but future
success.
Rob Etherington: Thank you. Thank you for the attention. And we appreciate the time to speak. [00:20:00]
