Q&A with Yuval Cohen, CEO, Corbus Pharmaceuticals

By Christiane Truelove • [email protected]

Yuval Cohen, Ph.D., CEO of Corbus Pharmaceuticals Holdings, spoke with Med Ad News about what the endocannabinoid system is, Corbus’ pipeline of drugs, and why he thinks there will be a flood of drugs targeting the endocannabinoid system.

Med Ad News: What is the endocannabinoid system? 

Yuval Cohen: A lot of people have not heard of it outside of our sort of fields. The endocannabinoid system is a central biological system. In all animal life, pretty much the moment you have a bunch of cells that hack together and declare themselves to be an animal, you can detect it. And it evolved at the same time. And alongside the two other systems that are much more famous – one is our central nervous system. And the other one is our immune system. And fundamentally, it basically talks to both of these systems. And the reason we have it is it was designed to help humans and other animals recover from trauma. 

So if you think about a caveman that gets mauled by a saber toothed tiger, he or she is lying in a cave, they’re bleeding, they’re in pain, they’re going into shock. They’re going to starve. They’re going to get infected, they’re going to get inflamed. All of those things. What kicks in and saves their lives, is the endocannabinoid system. It’s a system of little signaling molecules and the receptors they bind to. And what they’ll do, for example, to that caveman, is they’ll make the pain go away. That’s important. They will make the damage from the bite go away. They reduce inflammation, they promote tissue healing, cell remodeling, tissue remodeling. They will make sure that they don’t go into shock. So it’s antiepileptic. Interestingly enough, they will make sure that they’re not sad. If you think about it, if you get mauled by a tiger, I suspect you’re not going to be very happy. If you’re not happy, you’re going to die, right? So they’re euphoric. It makes you happy, it makes you not be sad. They’ll make sure you’re hungry. Because if you don’t eat, you’re going to die. So they give you the munchies. So this is a vast system that is very well understood that does a lot of things in the body. The big question is, what do you do with it that’s useful for a patient.

What we focus on is the inflammation part of it, as well as the metabolism part of it. And we actually don’t look at the plant at all. What are known as phytocannabinoids, which are plant-derived compounds, really have nothing to do with ours. And they [phytocannabinoids] tend to work well on the central nervous system, but not so well on these other systems. 

What we do is far more mundane. We work backwards, we look at the receptors in the body of the system. And like a lot of other pharma companies that focus on receptors, we literally invent compounds that bind to them. So, our compounds are not designed to make you happy. They’re not designed to give you the munchies, nor are they derived from nature. They’re good old-fashioned, small chemical molecules made by the pharmaceutical industry to focus on leveraging this system. 

Med Ad News: When you’re looking backwards from the receptors, what have you found, exactly, that differs the small molecule compounds from the plant-derived ones?

Yuval Cohen: So, the plant-derived compounds, THC, CBD, as I said usually the way they are used in medicine and for that matter, I guess in wellness, is that they are compounds that penetrate the brain very easily, they activate a cannabinoid receptor called CB1 primarily, and they do a lot of positive and sometimes entertaining stuff. 

So, for example, a drug like Marinol, which is basically a synthetic form of THC, if you have advanced cancer and are undergoing chemo, it will prevent you from vomiting, so, it’s an antiemetic, and it will make you hungry, because that’s important – anorexia is one of the side effects of chemotherapy. So the plant stuff, the way to think of it, is plant stuff equals pretty much brain stuff. If you look at Epidiolex, it’s a drug, it’s a plant-derived CBD that goes in the brain and prevents epilepsy, prevents epileptic fits.

What we do is very different. So we look at, we do two things. One, we look at the other receptor in the endocannabinoid system called CB2. And that receptor is not found in our nervous system, it’s found in our immune cells. And it is an anti-inflammatory receptor. So we develop novel anti-inflammatory drugs that are synthetic cannabinoids that bind to CB2, and they’re highly specific diseases. That’s where they really differ from the plant stuff. 

So that’s one program we have, that was in very late clinical stages. We obviously have had a bunch of setbacks. But overall, it looks like that drug does something. 

And then the big question there is, what is the next step for that drug? But it’s a completely synthetic compound. And it looks like and it acts like an anti-inflammatory drug. So we’re completely delighted. There’s another thing we do, which again, is very different to the plant. And that’s a different group of compounds that they bind to the CB1 receptors that we spoke about before, we’re talking about THC, for example, but instead of activating it, we actually do the opposite. We put it in reverse. And it’s really interesting.

 If you think about THC, it gives you the munchies, so you’re going to eat more food and you’re going to gain weight, and that’s normal. It’s actually what it’s designed to do. That caveman needs to eat calories and store them or he or she will die. What our drugs do is exactly the opposite. They turn your metabolism backwards so that you have less appetite, and you start to lose weight. You don’t store energy as fat. 

And what’s interesting about that story is if you go back 15 years, about four big pharma companies had late-stage CB1 targeting drugs for obesity. And one of them, which was from Sanofi actually, got to the market, it was called rimonabant. It got to the market in Europe. And it ended up being withdrawn because of brain-related side effects. 

Fast forward 15 years, we now have a second generation of these drugs that seems to be as efficacious but without the brain side effects. And so we may have a completely new generation of ant-obesity drugs, we’re really excited about them. 

And as an aside, obesity, which used to be an indication no big pharma wanted to pursue, in the last six months has become very, very sought after. Both Novo Nordisk and Eli Lilly are now moving their diabetes drugs into obesity. It’s suddenly the recognition that it’s not really a lifestyle issue necessarily, but really is a pathology, that has really taken off. And we will be the first company to target that, or re-target that, using the endocannabinoid system. 

Med Ad News: It’s kind of ironic that the whole research into the endocannabinoid system started because of the plant, but it’s gone in a totally different direction. 

Yuval Cohen: Absolutely. And you’re right. And in fact it’s really interesting because it started in the ‘70s. But almost no one in the U.S. could do research on it. And so a lot of it, for example, seminal research was initially done in Israel. … It’s unusual to find the biology in the body that is so exquisitely mapped, and well understood, and have almost no drugs associated with it. That’s very, very, very unusual. And it’s sort of a vacuum into which you would imagine at some stage, drugs would start to flow into.

Med Ad News: Except there is the whole thing of where do we start, and for some companies, it’s had to start with the plant. 

Yuval Cohen: Absolutely, there’s a whole universe there, companies that focus on phytocannabinoids, whether it’s THC or CBD, or increasingly some of its sort of rare phytocannabinoids or minor phytocannabinoids. But what you tend to see with those companies is by and by, they focus on central nervous system indications, and oftentimes, indications that fall under, for lack of a better word, psychiatry. Epilepsy, anxiety, autism, behavioral stuff, all of that is activating CB-1 in your brain. 

Think about CBD, everyone has heard of CBD. … So CBD you can actually make in two ways. There’s GW Pharma, where you literally have your own greenhouses, you grow the cannabis plant, and then you extract CBD and purify it, etc, etc. 

But there’s another way you can do it, which is you can actually make CBD in a chemical reaction. And there’s a big debate going on between which one’s better, and which one is cheaper. The advantage of a plant-derived CBD for example, is it tends to be very affordable. The plant is literally a weed, it grows like crazy. But the disadvantage that some would claim is purity. On the other hand, if you can make CBD in a chemical reaction, theoretically, it’s 100 percent pure, but it tends to be on the pricier side, for example, for things such as wellness, etc. 

Med Ad News: What are the next steps for Corbus and the company’s anti-inflammatory compound? And what are some other research programs that you are exploring? 

Yuval Cohen: So our pipeline is sort of very, very polarized. On the one extreme we have lenabasum, and that just completed a Phase III study. We didn’t hit the primary endpoint, but we’re certainly seeing signals of efficacy. The next step there is, we’re going to talk to FDA and just gain clarity from them. You know, what do they think about the data, etc, that’s really important. You know, we’re not in a vacuum. That compound is also in a Phase II study in lupus, and we should have that data by end of year. We’ll see how that goes. 

And then sort of the polar opposite of that is we have two synthetic cannabinoid programs, that are preclinical, they’ll start to go into the clinic end of next year. And those are, one is a CB1 targeting program in obesity. And the other one is a really interesting one, that will be fascinating to see how it unrolls, and that is a group of synthetic cannabinoids that bind to CB2, but are very different than our anti-inflammatory CB2 binding compounds. And they seem to have anti-cancer properties. There’s a huge literature talking about the endocannabinoid system in cancer. This has to do with the immune aspects of cancer. So it’s immuno-oncology. It will be fascinating to see what happens. We think at the end of the summer, around about the fall, we’ll have key preclinical data. And if that data is promising, then again, that’s a whole new class of cannabinoids that target cancer, and that could be really exciting. 

Med Ad News: Where do you think the future of endocannabinoid research is? 

Yuval Cohen

Yuval Cohen: I think the answer depends a lot on what your target audience is. So for example, and this is just my personal opinion, think about the fields such as wellness, nutraceuticals, cosmetics, etc. What we tend to do, as a society or as an industry, is we actually prefer using natural compounds. And almost by definition, those compounds cannot be overly potent, otherwise, that’s when the FDA steps in quite appropriately. I think for example, using synthetic compounds, rationally designed compounds, for those fields probably doesn’t make a lot of sense. With this side of it, the world we inhabit, which is the pharmaceutical world, it’s very rare to find natural compounds in the pharmaceutical world. There are exceptions. But they’re very, very rare. Because, scientifically, we know how to augment things, and make them, and alter them so that they’re much more potent. So I think again, the answer is, it depends on the industry and on the audience. 

You have a very, very well understood biology, exquisitely well understood. And yet you have this really weird, paradoxical situation whereby outside of the world of pharma, it seems that everyone is aware of this biology, sometimes it’s almost comically so. We took our cat to the vet, and the vet said, “You should give your cat CBD,’” and I just looked at her. The non-pharma world is very enthusiastic about this biology without actually understanding it. The pharma world understands the biology exquisitely. But there’s this weird gap between that biology and the drugs. I don’t think that’s sustainable. I think, probably sooner rather than later, we will see actual pharmaceutical drugs go into that vacuum. And at that stage, I think you’ll see a very significant transformation. 

Med Ad News: With Jazz Pharmaceuticals buying GW Pharmaceuticals, do you think this is an indication of where things are heading?

Yuval Cohen: Very much so. But even there, remember, that’s literally a phytocannabinoid. Next step from that is you go, “Oh, my goodness, I really understand how these receptors work. I understand what they do. Let me come up with a drug that actually does something for them.’” 

I think there is a 50-50 bet of the following – it’s either going to be from CB2 to inflammation, or CB1 in metabolism. And the reason I say CB1 in metabolism is because there was a drug approved for it. And back in the day, go back to Wall Street analysts’ estimates of the sales of rimonabant, they were clocking in at about $3 billion a year. This was going to be a massive drug.