180 Life Sciences: Developing Drugs To Tackle Distinct Inflammatory Diseases

180 Life Sciences was launched in 2020 by the merger of three companies. Members of the scientific team include Drs James Woody and Marc Feldmann, inventors of the rheumatoid arthritis drug Remicade®  (infliximab), Dr Larry Steinman, inventor of the drug Tysabri® (Natalizumab) for multiple sclerosis, drug discoverer Dr Jonathan Rothbard and Dr Raphael Mechoulam, discoverer of the human endocannabinoid system.

180 Life Sciences brings together the expertise of world-renowned scientists to develop and test novel treatments for inflammation and is currently working in both preclinical and clinical studies. The company’s preclinical work is exploring the use of synthetic cannabidiol (CBD) analogs as a treatment strategy for inflammation and pain, whilst clinical research is focused on repurposing anti-tumor necrosis factor (TNF) across different fibrotic conditions. Technology Networks recently spoke with Woody, chief executive officer at 180 Life Sciences, to find out more about the company's research and development pipeline.

Molly Campbell (MC): Why is inflammation one of the world’s largest drivers of disease?

James Woody (JW): There are 125 million people in the U.S. with chronic diseases; 30% of them have several chronic diseases at the same time. Many of these chronic diseases are driven by inflammation.

There are enormous numbers of patients around the world suffering with various inflammatory diseases. Some of them have more treatment options than others. This gives 180 Life Sciences an opportunity to have a substantial market in areas that have not been thought of before and that is our company’s focus.

There are 78 million people who suffer from rheumatoid arthritis worldwide. Ulcerative colitis, Crohn’s disease, systemic lupus, multiple sclerosis, psoriasis, Type 1 diabetes, non-alcoholic steatohepatitis, endometriosis and fibromyalgia are some examples of inflammatory disease which you have likely heard about in one way or another. Perhaps you even know people with some of these conditions. This is a very large market that has a lot of unmet needs that we can help to address.

MC: Can you talk to us about the history and mission of the company, what key research areas are being covered by 180 Life Sciences?

JW: Dr Marc Feldmann and I uncovered the fact that tumor necrosis factor (TNF) was a very inflammatory cytokine, when we developed the first ever anti-TNF drug, Remicade® (infliximab) which was effective in supressing the joint inflammation seen in rheumatoid arthritis. This happened while I was working as chief scientific officer at Centocor, and Dr Feldmann, with his colleagues, did the early informative clinical trials. We are the group that discovered the therapies that are currently available for rheumatoid arthritis, Crohn’s disease and psoriasis. We have now taken these discoveries forward and have several programs where we use anti-TNF to treat diseases that, before now, have not been thought to be related to TNF. For example, our programs in treating fibrotic diseases, such as in Dupuytren's contracture, and frozen shoulder. While not related to fibrosis, we think TNF can cause post-operative cognitive dementia.

Our scientists have made new discoveries and have shown that these diseases are amendable to anti-TNF therapy. We have a lot of data and science to support this and we have patented all of the related research.

All three of these programs are related to anti-TNF and that is why they are under our umbrella. We are using anti-TNF to treat these conditions.

MC: Please can you tell us about the fibrosis and anti-TNF program?

JW: Our scientists, Drs Jagdeep Nanchahal and Feldmann, amongst others, discovered that certain fibrotic diseases were driven by TNF. No one had thought of this before. For example, in Dupuytren's contracture, the condition starts out as a small nodule in the patient’s palm and eventually forms a fibrous cord that pulls their fingers together until surgery or several other kinds of therapies are eventually required. The scientists found that the entire fibrotic process was driven by TNF, and that anti-TNF would block the process. At 180 Life Sciences, we are treating patients to prevent the serious disabilities that will form if fibrotic conditions go untreated. For example, my wife had Dupuytren’s contracture and she spent a year experiencing difficulty moving her fingers and had to have surgery. Our 181 patient Dupuytren’s trial with anti-TNF is fully enrolled, and we will have results in quarter three-four. 

Another fibrotic condition we target is frozen shoulder, which is extremely painful. It leads to immobility of the shoulder and eventually patients require surgery. We think that the fibrosis process in the shoulder joint shares similarities with that of Dupuytren's contracture because ~50% of these patients also have a diagnosis of Dupuytren's. As the underlying mechanism for both conditions is identical, we believe it may be possible to prevent the pain and the disability in frozen shoulder by treating patients with anti-TNF.

The third program, while not fibrosis driven, is post-operative cognitive dementia, or POCD. Here, our scientists have discovered that during surgery, especially during emergency hip replacements or coronary artery bypass graft surgeries, TNF is released into the body and travels to the brain where it causes certain areas of the brain to become inflamed. POCD dementia is seen in ~30% of patients following these surgeries. Unfortunately, some of these patients never recover and can end up in nursing homes. We think that anti-TNF may prevent this, and so we are planning a clinical trial to further investigate this hypothesis.

All three of these programs, two of them relating directly to fibrosis and one of them to preventing a post-operative cognitive decline, are within our expertise.   

MC: Your pipeline includes synthetic cannabidiol (CBD) analogs (SCAs). Please could you tell us more about this program and what these compounds are?

JW: We are working with scientists in Israel that includes Dr Raphael Mechoulam who discovered the endocannabinoid system in humans. In the human body, there are two cannabinoid receptors. The first is CB1, which is largely found in the brain. When the CB1 receptor is stimulated it causes the psychosis that is seen with some cannabinoid molecules (e.g., delta-9-tetrahydrocannabinol). The second receptor is called CB2, and while it does reside in the brain, this receptor is predominantly found in the immune and gastrointestinal systems. The compounds that we are making synthetically are pure and specifically bind more to the CB2 receptor and they seemingly modify the immune system to reduce inflammation and pain.

Currently available cannabis-derived products can contain well over 100 different compounds, rather than containing purified, single cannabinoid compounds. At 180 Life Sciences, we are making a synthetic single version of CBD that is formulated to improve efficacy and bioavailability and will bind mostly to the CB2 receptor. The researchers have found that if you treat laboratory animals that have inflammation with one of these compounds the inflammation and pain is reduced.

We are planning to treat patients with inflammation using our synthetic CBD compounds. We are in the process of selecting our SCA candidate and currently have two or three lead candidates. We are planning to initiate IND-enabling studies likely beginning in early 2022.

Laura Lansdowne (LL): Can you tell us more about their method of action and how this makes them a potential strategy for treating inflammation and pain?

JW: Their exact mechanism of action is not currently totally understood. We know that binding to the CB2 receptor does modify the activity of immune cells and inhibits the inflammation and the pain. They may also bind elsewhere, to targets that we have not yet discovered, but this is something we are working on addressing.

We think we will be able to identify molecules that will be specific and potent. Even though we may not know exactly how they work, we have a good idea. Feldmann, Mechoulam and their colleagues are currently working to identify what the biochemical pathways are. Stay tuned, and I am sure a year from now we will be able to provide further details.

LL: What advantages are there to using man-made derivatives of CBD compared to naturally derived CBD?

JW: Naturally derived CBD that you can purchase over the counter may contain many different compounds. While some of them do what you want, perhaps pain relief or achieving psychological effects, we do not want them to be psychogenic. We want the synthetic CBD derivative to be orally available and non-addicting. We also want it to be specific as to avoid any of the side effects that might be seen with current herbal compounds. We are focusing very specifically on inflammation and pain. Patients with rheumatoid arthritis who are receiving anti-TNF with limited success, is an example of a subgroup that may benefit form synthetic CBD products.

James Woody was speaking to Laura Lansdowne, Managing Editor, and Molly Campbell, Science Writer, for Technology Networks.