Astellas Pharma said today it has acquired Quethera, a developer of gene therapies for eye disorders, for up to £85 million ($108.5 million), in a deal that expands the buyer’s efforts to build a pipeline of treatments for ocular disorders.

Based in Cambridge, U.K., Quethera has developed an ophthalmic gene therapy program designed to treat glaucoma and other conditions affecting the optic nerve. The program uses a recombinant adeno-associated viral vector system (rAAV) designed to introduce therapeutic genes into target retinal cells.

The targeted cells produce beneficial proteins to combat disease following treatment, which is designed to be administered as a single injection on one occasion into the affected eye. Quethera says its therapy is intended to provide long-lasting therapeutic benefits without producing a large inflammatory response after injection.

“We believe the rAAV program has potential as a new therapeutic option for the treatment of refractory glaucoma through an intraocular pressure-independent mechanism. It would address a high unmet medical need in glaucoma patients who are at risk of losing their eyesight,” Astellas President and CEO Kenji Yasukawa, Ph.D., said in a statement.

Quethera’s lead gene therapy, QTA020V, is designed to act via the neurotrophin Brain Derived Neurotrophic Factor (BDNF) signaling pathway. The company has cited past studies that showed patients with glaucoma having been observed to have reduced serum levels of BDNF compared to controls without glaucoma.

The studies also showed that QTA020V can efficiently transfect retinal ganglion cells (RGCs), elevate levels of mBDNF and the tropomyosin receptor kinase B (TrkB) receptor, and protect against TrkB loss.

Positive Preclinical Data

At the 2017 Association for Research in Vision and Ophthalmology (ARVO) conference, Quethera presented positive preclinical data showing that its lead candidate QTA020V resulted in a 61% reduction in RGC loss in a widely used experimental model of glaucoma.

The company also presented two posters detailing the design and initial testing of the gene therapy constructs in vitro and in vivo. The posters showed that the transgene was efficiently processed into two separate proteins that significantly increased RGC survival in two different animal models of optic nerve injury.

In a chronic ocular hypertension in vivo model, RGC survival in QTA020V-treated animals rose from 46% to 84% in the peripheral retina, the region most susceptible to glaucoma damage in humans. A second acute nerve crush in vivo model showed 67% more surviving RGC than control vector injected eyes.

“This deal enables us to accelerate our evaluation of this investigational technology program to see if we can slow or prevent disease progression for these patients,” added Quethera CEO Peter Widdowson, Ph.D.

Dr. Widdowson founded Quethera in 2013 to commercialize initial research by Keith Martin, D.M., MRCP FRCOphth, professor, ophthalmology at the University of Cambridge.

In 2015, Quethera received an undisclosed amount of seed funding from the Rainbow Seed Fund (since renamed the U.K. Innovation and Science Seed Fund [UKI2S]) and Cambridge Enterprise, the commercialization arm of the University of Cambridge. A year later, Quethera received a grant of undisclosed amount from the Wellcome Trust Pathfinder Award Scheme.

Building Eye Disorder Pipeline

The Quethera acquisition is Astellas’ latest move to build a pipeline of gene and cell therapies for eye disorders. The lead clinical product in that pipeline is ASP7317, a Phase II Retinal pigment epithelium cell therapy in development for dry age-related macular degeneration and Stargardt’s macular degeneration.

As of August 1, Astellas was recruiting patients for a planned 150-participant trial (NCT03178149)  that will combine a Phase Ib dose escalation evaluation of safety and tolerability, and a Phase II proof of concept study of efficacy and safety of ASP7317 for atrophy secondary to age-related macular degeneration.

In 2014, Astellas launched a research collaboration with Constance L. Cepko, Ph.D., professor of genetics, department of genetics, at Harvard Medical School focused on discovering the pathologic mechanism for retinitis pigmentosa and identification of new therapeutic targets.

In 2016, Astellas completed its $379 million acquisition of Ocata Therapeutics, surmounting opposition from Ocata shareholders who sought a higher price from Astellas. Ocata brought Astellas a “regenerative ophthalmology” approach designed to treat eye diseases by identifying cell types that are compromised or lost due to disease, then replace those missing cells with the same cell generated from a stem cell source.

Also that year, Astellas agreed to license from Clino worldwide development and commercialization rights to another eye disorder gene therapy program, an AAV-modified Volvox channelrhodopsin-1 (AAV-mVChR1) designed to treat retinitis pigmentosa. The value of that deal was not disclosed.

Astellas agreed to pay up to £85 million ($108.5 million) in upfront and milestone payments for Quethera. Following the closing of the transaction, Quethera became a wholly-owned subsidiary of Astellas.

Astellas said the acquisition is expected to have an “immaterial” impact on its financial results for the current 2018 fiscal year, which ends on March 31, 2019. According to its guidance to investors, disclosed April 26 and restated on July 27, Astellas expects to see its sales dip 1.7% over the previous fiscal year, to ¥1,278 billion ($11.5 billion), and its core operating profit decline 2.5% year-over-year to a projected ¥262 billion (about $2.4 billion).

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