Advancing analgesics

Antibe Therapeutics publishes research demonstrating enhanced pain relief and increased safety of ATB‐352

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TORONTO—Antibe Therapeutics Inc. has announced the publication of a multi-national study, entitled “Enhanced Analgesic Effects and GI Safety of A Novel Hydrogen Sulfide‐Releasing Anti- Inflammatory Drug (ATB‐352): A Role for Endogenous Cannabinoids.” The article was published in Antioxidant and Redox Signaling.
ATB-352 is a hydrogen sulfide-releasing derivative of ketoprofen, one of the more potent non-steroidal anti-inflammatory drugs (NSAIDs) commonly prescribed for severe pain. But ketoprofen is also known to be highly damaging to the gastrointestinal (GI) tract. ATB-352 is being developed by Antibe as a GI-safe and non-addictive alternative to opioids for the treatment of post-surgical pain.
“ATB-352 was significantly more potent as an analgesic than ketoprofen, and did not elicit GI damage. Pretreatment with a cannabinoid receptor-1 antagonist (AM251) significantly reduced the analgesic effects of ATB-352,” notes the article abstract. “The CB-1 antagonist exacerbated GI damage when co-administered with ketoprofen, but GI damage was not induced by the combination of ATB-352 and the CB-1 antagonist.”
The article reports on a series of studies which demonstrate that ATB-352 induces much greater pain relief than ketoprofen in an animal model of surgical pain. ATB-352 was also tolerated more easily in the GI tract. The pain-relieving potency of ATB-352 compared to ketoprofen was greater than 3-fold. Mice receiving ketoprofen exhibited a dose-dependent increase in the severity of bleeding ulcers in the stomach and intestine. In contrast, no GI damage was observed in mice treated with ATB-352, even at high doses.
The research team also identified a mechanism of action that explains the increased pain-killing effects of ATB-352 compared to ketoprofen. In addition to blocking the production of pain-promoting prostaglandins, ATB-352 further reduced pain by significantly elevating levels of naturally occurring endocannabinoids, in comparison to the levels of endocannabinoids observed in mice treated with ketoprofen.
The study was led by Dr. John Wallace, Antibe’s chief scientific officer, and included internationally recognized researchers from the University of Calgary, Canada; the University of São Paulo, Brazil; the University of Campinas, Brazil; and Umea University, Sweden.
Back in August, Antibe Therapeutics provided an update on its Phase 2B study for its lead drug ATB-346. The clinical study began in March 2019, and is designed to validate the efficacy of ATB-346 in reducing pain and establish the dose for Phase 3 development. A total of 360 patients with osteoarthritis of the knee are being randomized to either placebo or one of three doses of ATB-346 administered once daily: 150 mg, 200 mg or 250 mg.
“We have designed our clinical trial in a rigorous way and have been successful to-date in recruiting suitable patients to ensure a robust set of data. Although this has mildly delayed our timelines, we view data quality as paramount for this trial,” stated Dan Legault, Antibe’s chief executive officer, in a press release. “With the recent successful financing, we’re adequately capitalized to complete the trial while funding continued development of our other programs, and anticipate being in a strong position to negotiate potential partnerships upon a successful study outcome.”
An update by the company in November said that their Phase 2B study evaluating ATB-346 has surpassed 70% total enrollment. Patient recruitment has accelerated due to several initiatives, including the activation of five additional clinical sites, for a total number of 40 clinical sites — the largest number of sites for any clinical trial ever conducted in Canada.
“We’ve taken extra measures to expedite the completion of enrollment, but with the inevitable slowdown during the holiday season, we are pushing our guidance for top-line data to calendar Q1 2020,” noted Legault.

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