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Private Australian biotech Spinifex Pharmaceuticals is hoping to carve a niche in neuropathic pain by developing compounds in a largely overlooked application for angiotensin II antagonists. The class has generated multiple blockbusters based on its ability to lower blood pressure; however, the company is hoping its selective targeting will show effectiveness in relieving pain resulting from shingles, diabetes and chemotherapy.

Spinifex has a fully enrolled phase II study in post-herpetic neuralgia (PHN) that it hopes will report data by the end of the year, and is preparing a trial in chemotherapy-induced neuropathy for its lead compound,  EMA401, that should generate results next year. PHN is a competitive field with Pfizer’s Lyrica a well-established branded product,  gabapentin formulation  Horizant just receiving approval and generic  lidocaine and  gabapentin in  heavy use; nevertheless, Spinifex thinks it has spotted an opportunity with a novel mechanism of action.

“Even Pfizer’s own literature says that treatment works at best in one out of two patients and it might be closer to one out of four,” chief executive Tom McCarthy tells EP Vantage. “Either they can’t tolerate the CNS side effects or they just fail to respond.

“We’re targeting people that either would like to do EMA401 on top of a standard of care because they’re not getting adequate pain relief and they want something to give them further pain relief; or we’re targeting patients who either don’t respond to the standard of care or can’t tolerate the side effects,” Mr McCarthy says. “Initially [EMA401] would be a second-line drug. If the efficacy is there and the side effects aren’t there you could see how it could transition to first line.”

Painfully slow progress

The lack of efficacy of established drugs is a sign of how difficult the pain space is, but the company hopes it can identify a more effective treatment in some conditions with an unmet medical need. This might be a big task, but the hopes lie in a known but unused mechanism of action.

As work in the renin-angiotensin system was under way in the 1980s and 1990s, it was discovered that it was the AT1 receptor that had the biggest effect on blood pressure control, Mr McCarthy says. The AT2 receptor was found to have no effect and was set aside, but work done by Professor Maree Smith at the University of Queensland found that blocking  AT2 could have an effect on pain pathways; Spinifex now holds that intellectual property.

“It’s a known receptor but people haven’t been able to describe a human therapeutic use,” he says. “People think we’re somehow doing a repurposing of a hypertension medicine for neuropathic pain, but we’re just working on a similarly named but unique approach to neuropathic pain. So we hope being first in class offers the benefit to treat people who either have not responded to therapy or can’t tolerate the CNS side effects.”

Beyond PHN and chemo-induced neuropathy, the company is trying to refine its approach to a trial in diabetics with neuropathy, most likely in early-stage patients in whom the pain is related to microvascular damage, rather than later stage where nerve demyelinisation might be an issue. Meeting with clinicians during the BIO international meeting this week could help the company design a trial that can identify the patients most likely to respond, Mr McCarthy says.

Spreading the funding net

The BIO meeting may also help the company identify more funders for continuing into late-stage work. Spinifex is so far supported by two rounds from the Australian funds GBS Venture Partners, Brandon Capital Partners, Uniseed and Uniquest, totalling A$22m ($22.2m). Mr McCarthy says the company has sufficient capital to last into 2013, at which point it hopes to have established proof of concept in at least one indication.

A third venture capital round “would invariably involve US or European syndicate partners” to help the company better understand the opportunity offered by its product, Mr McCarthy says. Initial partnering discussions have also taken place with big pharma companies; however, he says a pivotal trial in PHN may require only 250 patients over 12 weeks of treatment, which the company believes is achievable with funding from a series C investment round along with mid-stage work in  chemo patients and diabetics.

The remainder of the year will be focused on producing results in the PHN trial, which could come as soon as the meeting of the International Association for the Study of Pain meeting in August, and dosing the first chemo patients in a study based in the UK, Mr McCarthy says.

“We think pain needs new mechanisms, better therapy and therapy without CNS side effects. We hope we’re doing something nobody’s thought of before,” he says.