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The key to innovation is seeing opportunity in unlikely places. For Antibe Therapeutics, the place is a cloud of noxious gas; the prize is a new generation of painkillers.

In the wake of the opioid crisis, there is an urgent need for safer analgesics. Almost one-in-10 Canadians prescribed opioid medications report problematic use. Meanwhile, non-addictive pills such as ibuprofen and aspirin belong to a class of therapeutics called nonsteroidal anti-inflammatory drugs (NSAIDs) that can have dangerous side effects — including gastrointestinal bleeding.

Dr. John L. Wallace, Antibe’s founder and chief scientific officer, saw that hydrogen sulfide was the path to safer, non-addictive painkillers. After all, he was also the scientist who discovered how NSAIDs damage the stomach. Despite its reputation as a toxic gas that stinks like rotten eggs, research has shown that tiny quantities of hydrogen sulfide are naturally produced in nearly every cell in the body. It works to help stimulate blood flow, reduce inflammation and protect cells from damage.

The company has found a way to combine an NSAID and hydrogen sulfide into the same molecule. Once inside the body, the NSAID dulls the pain while the hydrogen sulfide gets to work protecting the digestive tract.

“Astonishing as it may seem, this unpleasant substance helps protect the gastrointestinal lining,” says CEO Dan Legault. “Making NSAIDs less harmful to the stomach and intestines is a very difficult problem. Most of the big pharma companies and many others have tried and failed, but we are really close to solving it.

Moving quickly and pivoting smartly

Antibe’s early data on its lead drug, otenaproxesul, was highly encouraging. It was effective and non-addictive. Crucially, it was also well tolerated by the digestive system. In a 14-day clinical trial, less than 3 percent of otenaproxesul users developed gastrointestinal ulcers, compared with 42.1 percent of people taking naproxen, a common painkiller.

In the summer of 2021, Antibe’s researchers were developing otenaproxesul for use in chronic conditions such as osteoarthritis. Then came an unexpected result: Elevated levels of a liver enzyme had been detected in several trial participants. Everyone was healthy, but Antibe halted the trial when a review of the data suggested the compound might be unsuitable for long-term use. “That was a bolt from the blue,” says Legault. “We had picked up the liver enzyme issue before, but only at much higher doses. It became clear we needed to investigate a new indication for the drug.”

Course adjustments are not unusual in biotech, but Antibe was particularly well set up to pivot rapidly. As a virtual biotech company, its small team of senior biotech professionals develops intellectual property and has recruited smart minds to its advisory boards (including a Nobel laureate), but it outsources all lab and clinical work. Unencumbered with such overheads, Antibe can move quickly to follow new scientific leads.

Within 10 weeks, its team had identified that otenaproxesul could be used to treat postoperative pain — a U.S.$13-billion market where opioids are still heavily prescribed— and had built a new development plan. The company started its clinical acute pain program in early 2022. If the results are positive, Antibe will determine whether the drug’s potency could be applicable to treat other acute pain conditions, including migraines, menstrual cramps, gout, dental pain, and traumatic injury, where non-opioid options are limited.

Antibe is also expanding its hydrogen-sulfide platform into treatment for inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease. The company aims to develop an alternative to steroids, biologics and other medications that are expensive and prone to serious adverse effects. Antibe is screening candidate molecules that could become therapies for these conditions.

Each day, nearly a million surgeries are performed globally. If all goes to plan, within a few years an alternative will be available that will lead to safer pain relief. Even if it is based on a smelly gas.

Antibe’s hydrogen sulfide platform builds on 30 years of research by its founder and chief scientific officer, Dr. John L. Wallace. Now an adjunct professor at the University of Calgary, Wallace has published more than 500 research papers and is one of Canada’s most frequently cited biomedical scientists in academic works.

“John is at the pinnacle of his profession,” says Dan Legault, CEO of Antibe. “His scientific contributions are on par with the best in the field.”

Wallace’s initial breakthrough came in the early 1990s when he uncovered why stomach ulcers form in some people who take NSAIDs, demonstrating that the cause was physiological response.

Interested in preventing this damage, Wallace became intrigued by the emerging concept of gaseous mediators that are naturally produced in some tissues and seemed to play important signalling functions.

“John had this quite simple but brilliant idea of attaching a molecule that releases nitric oxide to a drug in order to improve the drug,” says Legault. In 1996, Wallace co-founded NicOx, the first company to gain FDA approval for drugs based on gaseous mediator technology.

In the early 2000s, Wallace and his colleagues discovered that hydrogen sulfide, another gaseous mediator, had anti-inflammatory properties and could help preserve the mucus layer that protects the digestive tract. In 2009, he founded Antibe to begin the process of turning his scientific discoveries into safe and effective pain medications.

Nearly a million surgeries are performed globally every day — most require pain medication.

Antibe Therapeutics is targeting the $13-billion market in post-operative pain medication.

Founder: Dr. John L. Wallace
CEO: Dan Legault
Year founded: 2009
Capital raised: $124 million
Breakthrough: Building on decades of research, the firm is using hydrogen sulfide to create anti-inflammatory pain medications with fewer side effects.

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