INDICATION Osteoarthritis; to be broadened as supported by relevant data and regulatory filings to include all conventional markets for NSAIDs, including rheumatoid arthritis, ankylosing spondylitis etc.
PRODUCT DESCRIPTION ATB-346 is a hydrogen sulfide-releasing derivative of naproxen (naproxen is among the most commonly used, and most cardiovascular-safe of the NSAID class).
TARGET SEGMENT(S) AND MARKETPLACE NSAIDs are the most commonly used therapy for osteoarthritis, yet their use is associated with a high incidence of gastrointestinal ulceration and bleeding. NSAIDs are also widely used in a number of conditions, including rheumatoid arthritis, ankylosing spondylitis, and general pain reduction, with a similarly high rate of gastrointestinal ulceration and bleeding. It is well-accepted that patients with these conditions would benefit greatly from an effective, GI-sparing anti-inflammatory/analgesic agent such as ATB-346.
MARKET LEADERS The two most widely prescribed NSAIDs for treating chronic pain and inflammation associated with osteoarthritis are naproxen and celecoxib (Celebrex). A common method to assess the effectiveness (ie. pain relief) of analgesics is the WOMAC Index, a widely recognized set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip. WOMAC pain scores are graded on a 10-point or 20-point scale, with a score of 10 or 20 (depending on the scale used) representing the highest level of pain. Studies have provided evidence that the average reduction of WOMAC pain scores observed with both celecoxib and naproxen is ~4 units (using a 20-point WOMAC scale).(1)(2)
ATB-346 ADVANTAGES As the standard first-line treatment for osteoarthritis, naproxen and other NSAIDs are effective, but can induce gastrointestinal ulceration and bleeding in a high number of patients, with much higher incidence in patients with co-morbidities and in the elderly. In these patients, selective COX-2 inhibitors offer only a modest improvement in terms of GI safety, but their use is associated with significant cardiovascular toxicity (studies to-date suggest that naproxen is the most cardiovascular-safe of available NSAIDs). ATB-346 has been found not to cause significant GI injury in rodents and dogs, even at very high doses. Moreover, ATB-346 remained GI-safe when given to animals with compromised mucosal defence or with pre-existing ulcers – situations in which selective COX-2 inhibitors cause GI damage/bleeding in humans. It also remained safe when co-administered with aspirin, which markedly elevates the risk of GI damage/bleeding with COX-2 inhibitors. ATB-346 also did not elevate blood pressure when administered acutely to hypertensive rats, in contrast to a significant hypertensive effect with naproxen.
PHASE 2A EFFECTIVENESS STUDY Antibe received approval from Health Canada in March 2016 to conduct a Phase 2 trial of ATB-346 in patients with osteoarthritis of the knee. The primary endpoint of the study was the clinical assessment of pain measured at three time points over the 10 day course of treatment with ATB-346 at 250 mg once daily. Antibe announced successful completion of the trial on August 8, 2016 with results showing ATB-346 to be effective at reducing pain in osteoarthritis patients, and equal to or better than naproxen or celecoxib in comparable studies. The drug was also safe and well-tolerated. In this trial, a once daily dose of ATB-346 produced a reduction of the WOMAC pain score of 4.3 units on day 4, with a further decrease to 7.6 units on day 10, at a very high level of statistical significance in comparison to baseline pain (p<0.001). Published studies have provided evidence that the average reduction of WOMAC pain scores observed with the most commonly prescribed drugs for treating osteoarthritis  is ~4 units (see “Market Leaders” above).
PHASE 2B GI SAFETY STUDY Antibe received approval from Health Canada in August 2017 to conduct a Phase 2, double blind GI safety trial of ATB-346 in 244 healthy volunteers. The study was designed to demonstrate the superiority of ATB-346 in GI safety compared to naproxen, the most prescribed nonsteroidal anti-inflammatory drug (“NSAID”) in the USA. One group was treated for 14 days with ATB-346 (250 mg once daily) while the other group was treated for 14 days with the standard prescription dose of naproxen (500 mg twice daily). The primary endpoint for the study was the incidence of gastric or duodenal ulcers of at least 3 mm diameter with unequivocal depth, considered the gold standard in assessing the GI safety of NSAIDs. On March 20, 2018, Antibe announced that ATB-346 successfully met the primary endpoint in the study. Subjects on ATB-346 exhibited an ulceration rate of 2.5% (3/118) versus an ulceration rate of 42.1% (53/126) for subjects on naproxen at the end of the treatment period, with a very high degree of statistical significance (p<0.001). ATB-346 was also safe and well tolerated.

(1) Boucher, Martin. A Bayesian Meta-Analysis of Longitudinal Data in Placebo Controlled Studies with Naproxen. Pfizer.
(2) Wittenburg et al. First-dose analgesic effect of the cyclo-oxygenase-2 selective inhibitor lumiracoxib in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled comparison with celecoxib. Arthritis Research & Therapy Vol 8 No 2 (2004).