UK biotech Heptares Therapeutics Ltd. on May 31 signed its third agreement with a Big Pharma company in six weeks, this time with AstraZeneca PLC.

The two companies have entered into a four-year research collaboration to discover and develop new medicines that target G-protein coupled receptors (GPCRs). AstraZeneca will have worldwide commercial rights to product candidates emerging from the collaboration, with Heptares receiving $6.25 million in unconditional upfront payments plus committed research funding and future milestones. Heptares will also receive royalties on product sales.

Research teams drawn from both companies will focus on a number of GPCR targets known to be linked to CNS/pain, cardiovascular/metabolic and inflammatory disorders.

The deal brings to more than $13 million the total upfront money that Heptares has received from its pharmaceutical partners this year, which together add an extra 18-20 months to the biotech's cash runway, according to CEO Malcolm Weir. It also represents further validation for the four-year- old company's technology.

GPCRs are widely known to be involved in disease; indeed, about a fifth of all currently-marketed drugs interact with GPCRs. But designing products that specifically target GPCRs is tricky, because these receptors, which span the cell membrane seven times, are highly unstable when removed from their cellular environment. Heptares' technology makes a small number of point mutations in the GPCR molecule, making it more stable, and thus easier to design drug targets against.

AZ Seeking Both Large and Small Molecule Candidates

After initial screening and lead identification by discovery teams at Heptares and AstraZeneca, results will be combined into a common pool and the best compounds taken forward in a collaborative joint effort for optimization. AstraZeneca will then select small- and large-molecule candidates for preclinical and clinical development.

That AstraZeneca is modality-agnostic in this deal - purporting to seek both small- and large-molecule candidates - reflects the growing importance of the Big Pharma's MedImmune biologics subsidiary within its overall R&D operations. Acquired in 2007 but left largely to its own devices given the biologics focus, MedImmune's R&D has recently been more tightly integrated with AZ's small molecule discovery efforts, including via the creation of two therapy-area-focused Innovative Medicines units (iMEDs) that span both small and large molecule R&D, in Cardiovascular and Gastrointestinal diseases, and in CNS and Pain.

The deal with Heptares will involve both these integrated iMEDs, as well as the Respiratory and Inflammation iMED.

According to AstraZeneca's Head of Discovery Enabling Capabilities and Sciences, Mike Snowden, Heptares' technology, which he said had evolved into a real drug-hunting platform since the company was first spun out of the U.K's MRC Laboratory of Molecular Biology in 2007, is uniquely applicable across the broad super-family of GPCRs. Thus, it should help AstraZeneca design drugs across a broad range of targets. Snowden is also confident the technology will be as valuable for generating GPCR-targeted large molecules like antibodies as it will be in creating small-molecule therapeutics.

Multitarget Versus Single Target Deals

Heptares' Weir was keen to differentiate the latest deal with AstraZeneca from those signed with Takeda Pharmaceutical Company and Shire PLC in previous weeks. "The two previous deals were single-target or single-compound, while the AZ deal is multi-target," he said.

The $100 million Takeda deal involves characterizing a specific GPCR believed to play a role in CNS disorders, with Heptares and Takeda researchers collaborating to generate leads Also see "Takeda To Hunt For New CNS Therapeutics With Heptares' Technology" - Pink Sheet, 11 April, 2011.).

The Shire deal involves that company taking an exclusive option on a novel adenosine A2 antagonist currently in preclinical development. No financial details of that deal were disclosed Also see "Shire To Strengthen CNS Focus With Option On Heptares' Novel Parkinson's Therapy" - Pink Sheet, 9 May, 2011.).

Transformational For Heptares

Notwithstanding Heptares' partnering success this year (adding to the one partner, Novartis SA, that it had previously), Weir is keen to emphasize that the biotech is more than a provider of drug discovery services. Like most other biotechs, it needs large partners' money and validation, but is also striving to develop its own product pipeline, in this case in CNS and metabolic diseases. The company is working on half a dozen potential targets.

Weir describes the company's partnerships as a means to extract value from the company's technology in areas where Heptares has no interests. But with funding hard to come by, deals with pharma firms, although in theory a side-show, are increasingly critical to biotechs' survival. Certainly Heptares' investors, including MVM Life Science Partners, Clarus Ventures and the Novartis Option Fund, who last provided $30 million in capital in February 2009, won't be discouraging more deals.

- John Davis (j.davis@elsevier.com)

U.K's Heptares Signs Up AstraZeneca In Latest GPCR-Focused Discovery Pact

More from Archive

More from Pink Sheet