Spinifex Pharmaceuticals is a clinical-stage biotechnology company specialising in the development of products for the treatment of pain.

Drug Discovery

Spinifex's AT2 Receptor Antagonist Technology: Concept to Clinical Success

Historical Perspective on the Discovery of the AT2 Receptor

The angiotensin II type 2 (AT2) receptor was discovered in the late 1980s/early 1990s during the search to find molecules that blocked the binding of angiotensin II (ang II) to what at that stage was thought to be a single type of receptor(1). During this medicinal chemistry process, scientists at companies such as Parke-Davis and DuPont Merck discovered that the tissue they were using for their radio-ligand assays actually contained two main types of receptor that bound ang II, specifically the AT2 and angiotensin type 1 (AT1) receptors and that antagonists at only the AT1 receptor reduced blood pressure. A range of highly selective AT1 receptor antagonists have now been developed as medicines to treat hypertension (this class of medicine is referred to as ARBs)(2). Despite the success of marketed ARBs for hypertension, and while their developers were able to show that selective AT2 receptor antagonists had no effect on blood pressure, they were unable to identify a human pharmaceutical use for these compounds(3,4). The initial inventor of Spinifex's technology, Prof. Maree Smith (University of Queensland) and subsequently other researchers have shown that these AT2 receptor antagonists relieve symptoms in animal models of neuropathic and inflammatory pain(5,6).  Further pivotal EMA401 mechanism of action work led by Prof. Praveen Anand (Hammersmith Hospital and Imperial College London) has been published in the European Journal of Pain(7). Since then, Spinifex’s lead product, EMA401, has demonstrated its potential in a Phase 2 clinical trial, showing a significant and clinically meaningful reduction in pain in patients with postherpetic neuralgia, a debilitating condition that can follow shingles(8).

AT2 Receptor Drug Discovery Program

In parallel with the clinical development of EMA401 for chronic painSpinifex has an active medicinal chemistry program aimed at the discovery and development of further highly selective AT2 receptor antagonists. These compounds are currently proceeding through hit to lead studies.

(1) VanAtten et al, Journal of Medicinal Chemistry, 1993, 36(25), p.3985-3992.
(2) Wexler et al, Journal of Medicinal Chemistry, 1996, 39(3), p.625-656.
(3) Steckelings et al, Peptides, 2005, 26, p.1401-1409.
(4) Porrello et al, Frontiers in Bioscience, 2009, 14, p.958-972.
(5) Smith et al, Pain Medicine, 2013, 14, p.1557-1568.
(6) Chakrabarty et al, Journal of Pain, 2013, 14, p.1053-1065.
(7) Anand et al, European Journal of Pain, 2013, 17, p.1012-1026.
(8) Rice, A.S.C. et al., The Lancet, Published Online, February 5, 2014.

Latest News & Events

11TH APRIL 2014  Spinifex Pharmaceuticals Raises US$45m in Series C Financing More

5TH FEBRUARY 2014  Results published in The Lancet show EMA401 is effective in reducing pain in postherpetic neuralgia More

25TH OCTOBER 2013  Spinifex's company profile featured in Nature BioPharma Dealmakers More