Takeda Pharmaceutical is paying Heptares £1.7 million (about $2.7 million) up front and will make a £2.8 million (roughly $4.5 million) equity investment in the U.K. firm as part of a drug discovery collaboration focused on a previously intractable GPCR target involved in CNS disorders. Under terms of the deal Takeda will retain worldwide rights to drugs emerging from the collaboration. Heptares could receive up to another $96 million in milestones, plus sales royalties.
GPCR drugs specialist Heptares will use its StaR® (stabilized receptor) platform to engineer thermally stabilized forms of the GPCR as the basis for drug discovery process. The firm will also apply structural biology and rational drug design technologies, including its Biophysical Mapping™ platform, x-ray crystallography, and fragment screening, to characterize the GPCR’s structure and generate early leads. Takeda will have responsibility for preclinical and clinical development of resulting candidates. “The Heptares platform applies broadly to the GPCR target family and delivers stabilized forms that most precisely capture the pharmacological conformations of GPCRs as they exist in their natural cellular environments,” comments Takeda CSO Shigenori Ohkawa.
The StaR technology generates stabilized GPCRs containing a small number of point mutations that improve thermostability without disrupting receptor pharmacology, Heptares claims. The resulting molecules are thus stable, functionally relevant, purified conformations of target GPCRs that retain their expected drug-binding characteristics. Heptares is exploiting the platform to generate new chemical templates for GPCRs that may overcome issues such as low selectivity, poor pharmacokinetic profiles, or toxicity that may be present in chemotypes identified by other means.
The firm has also developed its complementary surface plasmon resonance-based Biophysical Mapping technology, which can be used in combination with x-ray crystallographic data to provide additional structural data on StaR molecules and compound binding.
Heptares is using its platforms both in house and in collaboration with partners for the discovery of new GPCR-targeted candidates. An in house research-stage and preclinical pipeline is focused on GPCRs implicated in a range of disorders, including Parkinson disease/ADHD, insomnia, Alzheimer disease, schizophrenia, anxiety, type 2 diabetes, and cancer. Heptares also has a potentially $200 million ongoing drug discovery partnership with the Novartis Option Fund, centered on a Novartis target. In January Heptares confirmed generating a StaR molecule for the target.