Before being acquired by Johnson & Johnson (J&J) and becoming a well-known company, Centocor was a biotechnology company struggling to survive after the catastrophic failure of its sepsis drug candidate, Centoxin. Subsequently, immunologist Sir Marc Feldmann and the company's Chief Scientific Officer, Dr. James Woody, together conceived a trial that completely changed the company's fate.

Feldmann discovered that an immune system protein called tumor necrosis factor (TNF) drives tissue and joint damage in patients with rheumatoid arthritis. Meanwhile, Centocor had developed a TNF-blocking antibody, but it was shelved after also failing in sepsis patients.

From Wheelchair to Walking: A Trial That Changed the Landscape

"He and I designed a method to conduct a 20-patient anti-TNF treatment trial in rheumatoid arthritis patients," Woody recalled. "I sent him the antibody, and they immediately recruited the first 10 patients."

Like many patients with chronic autoimmune diseases at the time, all patients in the first trial group were wheelchair-dependent and had few other options to halt the destructive progression of the disease.

"We administered the first dose," Woody said. Within hours, patients felt better. "The next day, several of them actually stood up from their wheelchairs. Honestly, we were stunned; we never expected such a result."

The success of this trial foreshadowed the triumph of the blockbuster drug Remicade. As the first TNF inhibitor, Remicade was approved by the FDA in 1998. The following year, Johnson & Johnson acquired Centocor for $4.9 billion, an investment that paid off handsomely. Remicade generated over $50 billion in global sales and laid the foundation for numerous successful TNF inhibitors. Today, this class of drugs generates annual sales of up to $40 billion, led by AbbVie's Humira—the best-selling drug of all time. These drugs have also transformed the treatment trajectory of various autoimmune diseases, including Crohn's disease, psoriasis, ankylosing spondylitis, ulcerative colitis, and psoriatic arthritis.

Now, through the clinical-stage company 180 Life Sciences, Woody and Feldmann are applying anti-TNF drugs to entirely new tests.

The New Frontier of Anti-TNF

Although anti-TNF drugs have benefited many patients, Woody believes their potential is not yet exhausted. Today, Woody serves as CEO and director of 180 Life Sciences, with Feldmann as co-founder and executive co-chairman, working with other pioneers in the field to identify other diseases that might benefit from anti-TNF therapy while developing new drugs to suppress harmful inflammation.

The California company's most advanced anti-TNF program targets Dupuytren's contracture, a progressive hand disease. Its anti-TNF treatment uses a repurposed version of Humira and achieved positive results in a Phase 2b trial. Woody said the company is currently seeking marketing approval in the UK while also beginning discussions with the US FDA.

Dr. Jagdeep Nanchahal, chairman of the clinical advisory board and co-founder of 180 Life Sciences, was the first to identify the role of TNF in Dupuytren's contracture. The disease affects more than 12 million people in the US, initially presenting as one or more hard, painful nodules in the palm, sometimes followed by thick cords forming under the skin that tighten and pull one or more fingers inward.

"We have been successful in developing drugs and formulations in the past. We are satisfied with our current progress."

— Dr. James Woody, CEO of 180 Life Sciences

"You can no longer button your clothes, play an instrument, or type. It's a real disability," Woody said. "Before the fingers actually bend, patients have no therapy available."

By that point, patients may opt for needle aponeurotomy (a minimally invasive procedure that releases tight cords via needle puncture) or collagenase injections to improve finger mobility. But the condition can recur after surgery. Woody said they hope to completely halt this progression with a series of anti-TNF injections—an approach proven in the Phase 2b trial to effectively soften, shrink, or eliminate nodules.

The company is also testing an anti-TNF drug for postoperative cognitive decline—the confusion and memory problems that occur after major surgeries such as hip replacement or open-heart surgery, primarily in elderly patients. In about 15% to 20% of patients, this "cognitive fog" persists after surgery.

"A significant proportion of patients experience short-term dementia after surgery," Woody said. "Because the dementia persists, they end up in nursing homes."

Doctors once thought this was a side effect of anesthesia, but Nanchahal's research suggests it may be caused by TNF-driven inflammation invading the brain's cognitive centers. To test this theory, Woody said they are about to launch a Phase 2 trial, giving patients anti-TNF treatment before surgery to see if it can prevent the condition. The trial is expected to begin in the fourth quarter of 2023.

"This will be a fairly large trial involving hundreds of patients, some receiving saline and some receiving anti-TNF, and we will see if it truly benefits patients," Woody said. "If it works, it could become the standard of care for various major surgeries."

The third candidate indication for the anti-TNF program is frozen shoulder, a condition where the shoulder joint becomes encased in a stiff, fibrous tissue capsule, restricting movement. The condition affects about 9% of individuals aged 25 to 64 and has significant overlap with Dupuytren's contracture—patients often have both conditions. It can resolve on its own or improve with painkillers, physical therapy, or in rare cases, surgery. But this process can take a long time, sometimes up to three years.

"We plan to inject anti-TNF into the shoulder joint as soon as pain appears to see if we can block fibrosis and the formation of frozen shoulder," Woody said. The company recently halted a feasibility clinical trial for frozen shoulder launched in the UK due to low enrollment rates but hopes to move the trial to the US for better results.

The company is also conducting early-stage research to determine whether TNF is involved in liver fibrosis and nonalcoholic steatohepatitis (NASH)—the most severe form of nonalcoholic fatty liver disease. If the company can develop a successful treatment for this disease, which currently has no therapy, its potential market is estimated by Allied Market Research to exceed $20 billion. But Woody said it is not yet clear whether TNF is involved in NASH or how a treatment might target the disease.

"NASH is an interesting area, but it's far off because the research is still very preliminary," he said.

From TNF to Cannabidiol

Anti-TNF drugs are not the only way to suppress inflammation, so the company is also exploring synthetic CBD analogs derived from cannabidiol (CBD).

"We have shown that certain CBDs have anti-inflammatory and analgesic effects, so they are also anti-pain drugs," Woody said.

In recent years, CBD has gained popularity for its potential uses in pain, anxiety, and even insomnia. But plant-derived therapeutic agents have some drawbacks, including difficulty in oral delivery, dose standardization, purity assurance, and difficulty in determining drug absorption rates. The company is initiating pharmacokinetic studies of its oral CBD formulation to assess whether it can achieve stable doses needed to control inflammation and treat pain.

"Next, we will move into trials, using it as an anti-inflammatory and anti-pain drug," he said. "These will advance over the next year."

Also in early exploration is a potential mechanism targeting another pain receptor in the body, which Woody hopes could enhance the efficacy of anti-TNF drugs and reduce some side effects, such as increased susceptibility to infections. Given the team's past achievements, he is confident in achieving their goals.

"We have been successful in developing drugs and formulations in the past," he said. "We are satisfied with our current progress."