Inflammation represents one of the leading drivers of disease. Biotech company 180 Life Sciences is developing novel, anti-TNF therapies for treating distinct inflammatory diseases.
DocWire News spoke to James Woody, CEO of 180 Life Sciences, to learn more about the company, its mission, its treatment assets, and current clinical trials it’s involved in.
*Interview recorded in March 2022.
DocWire News: Can you give us some background on yourself, and the company, 180 Life Sciences?
James Woody: So by background, I’m a pediatric immunologist, and in my prior life, I was Chief Scientific Officer of a company called Centocor, which was one of the very early biotech companies. And we were the first ones ever to make a anti-TNF antibody and to test it in patients, and we were able to show that it was remarkably effective in patients with rheumatoid arthritis, Crohn’s disease and psoriasis and ulcerative colitis. And that actually began the pretty much the whole antibody based biologics industry. We were the first ones to do this with a humanized antibody.
I went on from there to run a pharmaceutical company called Syntex, former Syntex that was after Roche bought it and did that for eight years, we invented a lot of small molecules. And then I went on to start a company in oncology, cancer stem cells. And from there I went over to the dark side and joined a venture capital group and helped start companies for about 10 years and some of them are really successful. Some of them are okay and some crashed and burned, but that’s the nature of the business. And then more recently I helped start a couple companies on my own. And then I was approached by the founders of 180 LS to help them out and also to be CEO of their company, so that’s how I came to be CEO of 180 Life Sciences.
180 Life Sciences is repurposing anti-TNF for unmet needs. What is anti-TNF?
So in your body, you have lots of protein circulating around in your blood. These tell the body cells what to do, and some of them are called cytokines and cytokines are the ones that kind of tell your immune system what to do. And there’s quite a lot of these. And there’s some of them that are very good. There’s some of them that are bad actors and one of them is called tumor necrosis factor. It was named that totally by accident because it seemed to eliminate tumors in mice, but that’s never been able to be shown in humans, but the name has stuck with it. So tumor necrosis factor is the thing that causes some types of inflammation, if there’s an overproduction. For example, in rheumatoid arthritis, it’s the tumor necrosis factor that drives the destruction of the joints of your fingers and knees and shoulders and everything, so it’s a destructive cytokine. And what we did is we made a specialized antibody against TNF that binds it up and blocks it and prevents it from causing the inflammation. And that was the basis of infliximab or Remicade that we discovered from Centocor.
What is Dupuytren’s disease, how is it characterized?
Dupuytren’s Contracture is kind of a chronic disease, but it affects quite a lot of people, maybe 16 or 20 million in the US, same in Europe. It starts out as a small nodule in your palm. And over time, maybe a couple of years, some faster, some slower, it begins to form cords underneath the palm of your hand, it pulls your fingers together and contracts them. Sometimes this is inherited in families and sometimes it just occurs. So what happens is that this nodule starts, and as I said, over time, the fingers become contracted. So there’s no therapies for the early stage when the nodules just form, but that’s the basis of what we’re doing, I’ll talk about that in a minute.
Later on, after the fingers are already contracted and you have the disability, you can’t button your clothes, you can’t type with that hand. You can’t do many of the things that you like to do with your hand. There’s several therapies that they try. One of them is injecting a collagenase that’s partially effective, but they all, about half of those recur. You can try to disrupt these cords with a needle called needle aponeurectomy or alternatively, what happens is you end up going to surgery and they cut these cords out. Ironically, my wife had this and went through a whole year of steroid injections into her hand, finally had to have the surgery. So I’m familiar with the process. But that’s what happens, and I think people, as soon as the nodule forms, people these days, because they have Dr. Google, can immediately know what’s going to happen in the long run, so the information out there is quite impressive.
180 Life Sciences recently completed a Phase 2 study for Dupuytren’s. Tell us about the study protocol, the drug used and other updates on the study.
Our colleague in England, Dr. Jagdeep Nanchahal, was able to look at Dupuytren’s Contracture and especially the nodules, and through a series of very elegant experiments, he was able to show that the nodule was driven by the TNF, the bad actor. And in this case, the inflammation caused the fibrosis that we’re talking about, that leads to the finger contracture. And so he was able to work out that if you inject anti-TNF into this nodule, you can impact the course of the disease.
And so he did a very large trial of about 150 patients in the UK and was able to inject anti-TNF into the nodules of their hands. And in that trial, which took over a year, there were three or four injections, but we were able to show that both the primary and secondary endpoints of the trial were met and the endpoints had to do with the size of the nodule, whether it was growing, whether it was shrinking, whether it was harder or whether it was softer or whether the fingers were contracting, all of that, but we met the primary endpoints and the full publication with all the details will be out, hopefully in the next couple of months.
You have another trial planned for Frozen Shoulder. What is Frozen Shoulder, and how will the trial aim to address it?
Yes, Frozen Shoulder is another kind of inflammatory condition where fibrosis forms in the shoulder. And it initially starts out as being extremely painful. And that goes on for several months and then eventually the pain subsides, but the shoulder becomes totally immobile. And eventually you have to have surgery to remove the fibrotic tissues. Interestingly enough, this occurs more common in patients with diabetes, but about half of those patients also have Dupuytren’s. And so we think that the fibrosis in the Dupuytren’s and the fibrosis in the shoulder is the same mechanism. And so Dr. Nanchahal will be injecting anti-TNF into the shoulder very early, as soon as the pain is evident, then he’ll try to inject anti-TNF and maybe relieve the pain and also the formation of the fibrosis, so that one can avoid the surgery, which is actually quite expensive. And also, there’s quite a long course of physical therapy after the surgery, so it’s something you’d like to avoid. And so we’re trying to treat patients both with Dupuytren’s and Frozen Shoulder before the disability develops.
A third program, which is soon to be clinical, is anti-TNF for post-operative cognition delirium or POCD. Tell me about POCD, and the preliminary research that led the team to pursue this indication?
We know that now that they’re doing fairly aggressive surgery in older patients, either hip replacements or emergency hip corrections or CABG procedure, coronary artery bypass graft, or cardiac surgery, that a fair percentage of these people after the surgery, just have a foggy brain. And the fog goes on for some time and we call it postoperative cognitive dementia, as the technical term. And in some patients, maybe 15 or 20%, it doesn’t go away. And they end up in nursing homes and they actually don’t live very long after that. And so our colleagues in the UK, Dr. Nanchahal and Dr. Feldmann and his colleagues, have shown that during the surgery, any kind of aggressive surgery, that TNF is released from the tissue damage, and the TNF goes to the brain and opens it up and lets inflammatory cells get into the area of the brain that’s where your cognitive areas are, and so that leads to the dementia.
And in the past, they’ve thought this all had to do with the anesthesia, but we think it’s the TNF that’s actually causing this dementia going forward. And so we’re actually going to do a trial in patients that are having their hip repaired that are older, and we’re going to administer one dose of anti-TNF just before the surgery starts with a view towards preventing the dementia going forward. So this will be a long trial, but if it works, it’ll be something that everybody who goes into major surgery would want to have. So it’s another exciting opportunity for 180 LS and our investigators.
180 Life Sciences recently announced licensing of a compound called HMGB1. Tell us more about HMGB1 and the company’s plans for it.
The company is also working on other areas of fibrosis, not just Dupuytren’s Contracture and Frozen Shoulder, but other areas like liver fibrosis, which occurs with NASH. And we are working on ways to prevent that as well, much like we’re working on Dupuytren’s and Frozen Shoulder. The fibrosis in the liver is really hard to reverse, and there are no real agents that do that, but there’s a lot of people trying different things. Now what the HMGB-1 does, it doesn’t change the fibrosis, but once the fibrosis is stopped, it could help the liver cells to regenerate. So this is kind of a regenerative medicine. It makes the tissues regenerate, whether it’s heart or whether it’s liver or whether it’s lung or whatever. And so it’s going to be used after the fibrosis is stopped. And so that’s kind of what we’re interested in. And we’re just getting that program off the ground and making the initial compounds to do our testing.
Any closing thoughts?
Well, I’d like to talk about our team. The company was founded by Dr. Mark Feldmann, who was the one, he was the original person who figured out that TNF was causing the joint destruction and arthritis, and with he and I and others, that actually did the very first trials ever. And this was done in patients with wheelchairs, and they actually got up out of their wheelchairs and walked around. It was a phenomenal moment. We had no idea it would work that well. And some of them actually did a pirouette down some stairs. We have videos of this. So it’s kind of like The Awakening movie where they gave them the L-DOPA and they all woke up. Well, in this case, they got up out of their wheelchairs and there’s no patients in wheelchairs with rheumatoid arthritis in the whole world because of that drug, and the ones that followed on.
The current Humira from AbbVie is the preferred one. But the whole idea and concept, we started back then. Other founders, Dr. Larry Steinman, he and Mark put 180 LS together. And he developed Tysabri, the very first drug to help MS patients. And it was another phenomenal discovery that he made. And he’s also working on MS and other areas. But so we have the leaders in inflammation as the people who actually founded the company. So it’s a pleasure to work with them. I’ve been acquainted with them off and on for the past, maybe 25 years, so working with them again is a real pleasure.