ATB-352, our second pipeline drug, is a strong and non-addictive analgesic targeting the $11 billion market for post-operative pain.

ATB-352 is a hydrogen sulfide-releasing derivative of ketoprofen, one of the most potent NSAIDs prescribed for acute pain. However, ketoprofen is also one of the most damaging NSAIDs to the gastrointestinal tract. ATB-352 has been shown to be gastrointestinal-safe, highly effective and non-addictive in animal studies. Investigational New Drug-enabling studies for ATB-352 are underway.

Global Opioid Crisis

While opioids (e.g., oxycodone, fentanyl) are widely prescribed for acute pain relief, they are often abused due to their highly addictive nature. More than 60% of drug overdose deaths involve an opioid. With total mortality having quadrupled since 1999, more deaths are now attributable to opioids than to road accidents.

“On average, 130 Americans die every day from an opioid overdose.”
– Centers for Disease Control and Prevention

The misuse of prescription opioids costs the United States nearly $80 billion per year, including the costs of healthcare, lost productivity, addiction treatment, and criminal justice involvement.1

There is a widely recognized, urgent need for a safer, non-addictive pain-killer for post-operative pain.

Lead Indication: Post-operative Pain

The over-prescription of opioids is being driven largely by the lack of alternative therapies that are both safe and effective. Of the 50 million US surgical patients requiring post-operative pain medication each year2, 80% are prescribed opioids3, with more than 6% becoming persistent opioid users after surgery.4  In targeting the $11 billion market for post-surgical pain relief5, ATB-352 represents a compelling therapy given its analgesic potency, gastrointestinal safety and lack of abuse potential.

Many surgeries require a multi-day hospital recovery period, during which intravenous agents are often prescribed to manage post-operative pain. Upon discharge from hospital care, patients may continue to suffer from pain for several weeks. This transition can be challenging for both patients and physicians, who seek to prescribe an oral therapeutic that is effective but does not create addiction concerns. To address this, Antibe has adopted a two-stage product strategy to streamline pain management and to avoid changing medications during the recovery period:

      (i)  an aqueous formulation of ATB-352 for intravenous administration of ATB-352 while in hospital; and
      (ii) a oral tablet formulation of ATB-352 for patient use following hospital discharge.

In view of this drug’s potential to replace opioid use, Antibe will pursue an FDA Fast Track designation to expedite the development and regulatory approval process.

ATB-352: Non-addictive and Gastrointestinal-safe

In preclinical studies, ATB-352 caused negligible intestinal damage compared to ketoprofen, despite comparable suppression of intestinal prostaglandin or whole blood thromboxane synthesis.6  The rats were treated orally twice-daily for 5 days with either 10 mg/kg ketoprofen, or an equimolar dose of ATB-352 (14.5 mg/kg). Pharmacokinetic and toxicology studies suggest that ATB-352, like ATB-346, is effective when administered once daily.7

When tested over a concentration range of 3 to 30 µg/mL in a CEREP in vitro assay, no agonist effect of ATB-352 was found against the µ(MOP) opioid receptor, indicating no addiction potential.7

 


ATB-352 causes negligible gastrointestinal damage in rats compared to ketoprofen, a very strong NSAID prescribed for acute pain.

Enhanced Analgesic Potency and GI Safety Confirmed: A Role for Endocannabinoids

In early 2020, the results of a series of studies were published demonstrating that ATB-352 induces much greater pain relief than ketoprofen in a well characterized animal model of surgical pain.8   Despite the increased analgesic potency, ATB-352 was also much better tolerated in the GI tract, with the pain-relieving potency of ATB-352 greater than 3-fold compared to ketoprofen. 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 very high doses.8

A mechanism of action was also identified that explains the increased pain-killing effects. 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.8

1) Florence et al. The Economic Burden of Prescription Opioid Overdose, Abuse, and Dependence in the United States, 2013. Med Care. 2016;54(10):901-906.
(2) Transparency Market Research: “Post-Operative Pain Market: Overview”, 2016.
(3) Hill MV et al. Wide variation and excessive dosage of opioid prescriptions for common general surgical procedures. Ann Surg. 2017;265(4):709-714.
(4) Brummett CM et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg. 2017;152(6).
(5) Transparency Market Research: “Postoperative Pain Therapeutics Market – Global Industry Analysis, Size, Share, Growth, Trends,
and Forecast, 2019–2027″, 2018.
(6) Gemici et al. H2S-releasing drugs: anti-inflammatory, cytoprotective and chemopreventative potential. Nitric Oxide. 2015 Apr 30;46:25-31.
(7) Antibe pre-clinical data on ATB-352.
(8) Costa et al. Enhanced Analgesic Effects and GI Safety of A Novel Hydrogen Sulfide-Releasing Anti- Inflammatory Drug (ATB-352): A Role for Endogenous Cannabinoids. Antioxidant and Redox Signaling. 2020 Feb 16.

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