Antibe Speeds Hydrogen Sulfide-Releasing NSAID Development
Executive Summary
Canada’s Antibe Therapeutics is accelerating the early-stage clinical development of new molecules that depend on the cytoprotective and signaling properties of minute amounts of hydrogen sulfide to have a potent anti-inflammatory and analgesic effect.
Developing a potential new class of non-steroidal anti-inflammatories and analgesics based on compounds that link a known non-steroidal anti-inflammatory drug (NSAID) with a hydrogen sulfide-releasing molecule might seem surprising, but that’s exactly what Canada’s Antibe Therapeutics Inc. intends to do, through global partners.
In large doses, hydrogen sulfide is a gas with an unpleasant smell, but in much smaller, physiological amounts, the molecule is believed to have cytoprotective properties, acting as an endogenous anti-inflammatory agent and signaling molecule. This approach is reminiscent of that involving another endogenous agent, nitric oxide, and indeed they have both been classified as gaseous signaling molecules, or gasotransmitters.
The Toronto-based and listed company already markets bone graft substitutes and other products for dental and orofacial surgeons through its subsidiary Citagenix Inc., but says it has decided to pursue the development and marketing of its potential novel pharmaceutical products through regional partners.
There is a plethora of generic, OTC and branded analgesics and NSAIDS available for mild to moderate pain and inflammation, including aspirin, paracetamol, ibuprofen, naproxen and diclofenac, but there is still an unmet need for drugs that are better tolerated gastro-intestinally and not associated with the development of gastric inflammation or peptic ulcers, particularly in higher doses. Drugs that could replace the use of opioids in chronic and severe pain are also needed.
Analysts at Datamonitor Healthcare confirm there is a strong demand for novel drug classes in the area of pain, particularly to address the $13bn US market for opioid analgesics, and notes that a variety of approaches are being explored in more than 300 clinical studies, led by companies like Pfizer Inc., Eli Lilly & Co., Grunenthal GMBH and Biogen. Some of the most anticipated agents in late-stage trials include Grunenthal’s cebranopadol, in Phase III for cancer pain (Also see "Grünenthal On Hunt For Asia Partner As Pain Killer Hits Phase III Endpoints" - Scrip, 3 Oct, 2016.), and Pfizer and Lilly’s anti-nerve growth factor MAb, tanezumab. (Also see "Pfizer/Lilly ready to ditch painful past with new tanezumab trials" - Scrip, 23 Mar, 2015.)
Proof Of Concept Studies
Following what it described as clinical results beyond its expectations in an initial Phase II study with lead compound ATB-346 last year, and a subsequent extensive review of its development strategy for the drug, Antibe Therapeutics says it will start a Phase II proof of concept and gastro-intestinal safety study in the next quarter, earlier than originally expected.
After completion of that study, it will start a Phase II dose-ranging effectiveness study and begin global partnering discussions, the company said in a statement released April 18. The Phase II GI safety study is expected to be completed at the end of 2017, and the efficacy study in the second quarter of 2018, said Antibe CEO Dan Legault.
In last year’s study, ATB-346 produced pain relief at a 250 mg dose that was as active as naproxen or celecoxib, a finding that has fueled the decision to try and quickly confirm the drug’s potency – the first Phase II will be in healthy volunteers and will compare ATB-346 with naproxen, with the primary endpoint being GI tract ulceration. The efficacy study will be conducted in 200 osteoarthritis patients.
ATB-346 consists of naproxen linked to a hydrogen sulfide releasing moiety, with the latter thought to act as a cytoprotective against naproxen-induced ulceration. Antibe additionally has ATB-352, a ketoprofen-based product also linked to a hydrogen sulfide-releasing moiety, in preclinical studies, and with potential as an analgesic for severe acute pain.