Shire stakes a claim

BOSTON—Working toward broadening its pipeline and acquiringfuture innovative therapies, global specialty biopharmaceutical Shire PLCrecently made two significant investments in potentially innovative treatmentprotocols. In early March, the company agreed to buy privately held FerroKinBioScience for an upfront payment of $100 million, plus potential milestonepayments of up to $225 million, in an effort to boost its hematology business.In addition, Shire also purchased the worldwide exclusive license for thedevelopment and commercialization of an adenosine A2A antagonist from UnitedKingdom-based Heptares to treat central nervous system (CNS) disorders.

Shire was strongly attracted to Ferrokin's lead product, apotential treatment for iron overload that is being studied in Phase IIclinical studies in patients who have received multiple blood transfusions.

In the agreement with Heptares, Shire has agreed to pay thecompany an upfront option grant, plus future development and commercialmilestone payments that could total $190 million, as well as royalties onproduct sales. Further terms of the agreement were not disclosed.

Jeff Jonas, senior vice president of research anddevelopment for Shire's Specialty Pharmaceuticals and Regenerative Medicineunit, says Shire is continuously searching for innovations that have thepotential to help the company develop differentiated medicines.

"This agreement with Heptares is a reflection of our growthstrategy of investing and focusing on highly targeted drug discoveryplatforms," Jonas says. "We are impressed with the novelty and quality of theA2A antagonist leads generated by Heptares, resulting from what we believe tobe the first time a structure-based drug discovery approach has been appliedfrom the beginning to a GPCR drug target."

Currently in preclinical development, adenosine A2A is aG-protein coupled receptor (GPCR) involved in the regulation of dopaminergicpathways in the brain. Inhibition of the A2A receptor is a validated mechanismin the treatment of CNS disorders, but Heptares has taken it one giant stepfarther by actually discovering and developing new medicines targeting GPCRs,which are linked to a wide range of human diseases.

Adenosine A2A, in fact, could eventually prove to be a newtreatment for a range of CNS disorders. While the specific CNS disease targetshave not been disclosed, similar rival drugs are already in development totreat Parkinson's disease.

Heptares already has development deals with Takeda,AstraZeneca, MedImmune and Novartis Option Fund, and has raised $40 million inventure financing from MVM Life Science Partners, Clarus Ventures, NovartisVenture Fund and Takeda Ventures.

Malcolm Weir, CEO of Heptares, tells ddn, "From Heptares' perspective, Shire is one of the world'sleading CNS specialty pharmaceutical companies—and the fit of productopportunity and company cultures was particularly good. Heptares aims to be theleading company that discovers and develops new medicines targeting GPCRs, andit believes its unique approach and capabilities will enable this through thedevelopment of a broad pipeline of drug candidates for serious CNS andmetabolic disorders, internally balanced with strategic alliances with pharmapartners. The upfront fees and potential profits will be used to execute thecompany's strategy and grow Heptares through its structure-based drug discoverycapabilities and advancement of its internal pipeline."

Heptares' discovery of entirely new types of chemicalstructures for inhibiting the A2A receptor and potentially possessingbest-in-class drug-like characteristics represents "a radical advance afterdecades of largely unsuccessful medicinal chemistry," Weir adds.

The major problems with CNS therapies are lack of efficacyand side effects that result from non-specific binding of sub-optimal smallmolecule drugs, he notes. Many CNS disorders can be traced back to GPCRactivity. GPCRs are key in signal transduction pathways.

"Heptares has overcome this major obstacle," Weir said. "Its technologycan stabilize GPCRs in pharmacologically relevant conformations and generatedetailed structural information that can enable drugs to be designedatom-by-atom, thus offering high potency and specificity, fewer side effectsand potential first-in-class or best-in-class drug opportunities."

Shire acquires Pervasis Therapeutics to bolster regenerativemedicine business

DUBLIN, Ireland—Shire PLC announced April 12 that it hassigned an agreement to acquire substantially all the assets of PervasisTherapeutics, for an undisclosed sum.

Per the company's announcement, Shire will provide Pervasiswith an upfront payment in addition to potential post-closing milestonepayments that are dependent on Shire's achievement of certain clinicaldevelopment, regulatory and sales targets.

According to Shire, the acquisition complements its 2011purchase of Advanced BioHealing and further demonstrates Shire's commitment toinvesting in and building out its portfolio of regenerative medicine therapies.

Pervasis' clinical development assets bring to Shire a newcell-based technology platform—endothelial cell technology—with potentialglobal opportunity. The company's lead program, Vascugel, addresses asignificant unmet medical need for acute vascular repair technologies focusedon improving hemodialysis access for patients with end-stage renal disease(ESRD). With diabetes being the global leading cause of ESRD, and accountingfor approximately 40 percent of ESRD patients in the United States, Pervasis'Vascugel therapy complements ABH's Dermagraft, which is indicated for diabeticfoot ulcers, a condition highly prevalent among diabetic dialysis patients.

Shire will initially focus on completing a Phase II programto address maturation and maintenance of arteriovenous (AV) access forhemodialysis patients, which will instruct a future development pathway.

"There are currently no approved therapies that directly targetthe underlying physiological processes associated with the creation of AVaccess sites in hemodialysis patients, including inflammation, thrombosis, andrestenosis," said Shire Regenerative Medicine President Kevin Rakin in astatement. "As a result, there remains a significant unmet need fortechnologies that improve hemodialysis access for patients with ESRD. Webelieve Vascugel has the potential to enhance the rate of blood vessel repairwhile also providing for increased maintenance of the access site for aprolonged period of time as compared to current treatments. This acquisitionmarks a very important step for Shire in building a Regenerative Medicinebusiness focused on tissue repair and regeneration."

The closing of the acquisition is subject to ancillary conditions.