EP Vantage Interview - Heptares keeps up deal pace with Astra discovery pact

Reinforcing its claim that its platform technology can hit targets that others cannot reach, Heptares has delivered a third development deal in seven weeks. The largest so far, the four year collaboration with AstraZeneca, comes with a $6.25m signing fee and “substantial” committed research funding by the pharma giant.

The deal follows pacts with Shire and Takeda, all struck to gain access to Heptares’ expertise with G-protein coupled receptors (GPCRs). The broad and largely untapped potential in these drug targets is attracting a lot of big pharma interest, Malcolm Weir, chief executive, tells EP Vantage.And it seems further deals from this young UK company, only founded only in 2007, are not out of the question.

Research effort

The collaboration with Astra will focus on specific GPCR targets in the fields of central nervous system and pain, cardiovascular and metabolic and inflammatory disorders. Both small molecule and biologics will be investigated, with both companies working together on discovery, and Astra solely responsible for preclinical and clinical development.

“Both companies are putting their lead discovery and optimisation forces to bear on these intractable targets that Astra has chosen,” Dr Weir says, with a “significant number” of Heptares staff set to work on the collaboration.

The private firm, a spin out of the Medical Research Council, currently employs 50 people – two years ago the employee roll stood at 12.

Under the deal Heptares could ultimately receive more than $188m in milestone payments plus royalties.


Despite being the most successful protein family for drug discovery to date, GPCRs are unstable when taken out of their cell membrane. As such, they are hard to characterise and screen. Dr Weir says that of the approximately 370 GPCRs on the human genome, only 75 have been validated as drug targets.

“But they still provide opportunities for finding much better medicines. It’s a gene family with some of the best in class and first in class opportunities,” he says.

Heptares StaR technology stabilises the GPCRs, allowing the company to deploy structure-based drug discovery techniques to identify new drug candidates.

“Targets that were otherwise intractable become tractable,” he says. “The productivity in terms of new targets in the GPCR space has been low in past decade. Only one new target has been drugged per annum in the last ten years and there’s probably ten times that number that people wish they could be drugging."

Long heritage

The deals delivered in the last few weeks demonstrate that big pharma are certainly interested in what Heptares has developed. Dr Weir says both Takeda and Astra have a long heritage in GPCR research and know where the problems lie.

Still, it will be some time before they know if Heptares has found the answer. None of its candidates have yet entered the clinic, although this seems to be only a matter of time now.

The compound that Shire has bought an option over is one of the most advanced, an adenosine A2A antagonist in pre-clinical development for Parkinson’s disease and other CNS diseases. Pre-clinical data that could trigger a full deal should be available within a year.

Meanwhile, the company has a number of internal molecules in late lead optimisation stage, in CNS and metabolic indications.

The two-year Takeda deal – which brought a £4.5m ($7.4m) upfront and a possible £60.5m in milestones – was another early stage discovery pact, to find leads in CNS indications.

An option deal with Novartis Option Fund has also been in place since 2009, over another specific but undisclosed GPCR target.

Strong position

The deals have left the company in a strong financial position, with no immediate need to find further funds, Dr Weir says. Meanwhile, interest in the platform remains high.

“We’re constantly talking to pharma,” he says, declining to say whether further deals are on the way. However, he believes more deals could be struck, without denting opportunities for the company in the future.

“We could do [more deals] without damaging our internal pipeline and enterprise value because there are so many GPCRs that are of interest to the industry,” he says.

“There’s a massive disconnect at the moment between what the industry wants to do and what it can do, and that’s what we’re selling.”

And so far, big pharma seems happy to keep buying.

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