Ophthotech adds to pipeline again as climb back continues

Ophthotech has signed two deals to bulk up its drug and gene therapy pipeline, following the demise of its lead wet age-related macular degeneration (AMD) candidate last year.

First up is the acquisition of Inception 4, a biotech backed by Versant Ventures, that gives Ophthotech rights to small-molecule inhibitors of HtrA1 (high temperature requirement A serine peptidase 1 protein) for age-related retinal diseases—and also makes Versant an Ophthotech shareholder with a 12.5% stake.

HtrA1 inhibitors could have potential in a number of diseases including geographic atrophy, a severe form of dry AMD, said Ophthotech CEO Glenn Sblendorio on a conference call. Work will start soon on the selection of lead compounds that can be formulated for delivery into the eye, with a view toward filing clinical trial applications in late 2020.

The second deal is an exclusive option on an adeno-associated virus program for a rare degenerative eye condition—Best disease—developed by the University of Pennsylvania (Penn) and the University of Florida Research Foundation (UFRF) that adds to its gene therapy platform.

Best disease, caused by mutation in the Best1 gene, affects around 10,000 people in the U.S. and main European markets and typically causes permanent loss of central vision. There are no approved therapies for the disease, according to Sblendorio, who said the current objective is to file for approval to start U.S. trials of the gene therapy in 2021.

In August 2017, Ophthotech was hit by a trio of failed trials that spelled the end of its lead gene therapy candidate Fovista and caused it seek out new retinal disease assets, hiring Leerink to weigh up its strategic options.

That left it the biotech complement C5 inhibitor Zimura (avacincaptad pegol) as its new lead, and Sblendorio said on the call that program remains on track for a data readout for wet AMD before the end of this year, for dry AMD in late 2019, and for Stargardt disease in 2020.

By the end of the year, data should be available from a phase 2 trial combining Zimura with Novartis’ established anti-VEGF drug Lucentis in patients with wet AMD who haven’t previously received VEGF-targeted therapy.

Meanwhile, Ophthotech’s phase 2b studies of Zimura as a monotherapy for geographic atrophy secondary to dry AMD and Stargardt—an inherited retinal orphan disease that causes vision loss during childhood/adolescence and affects an estimated 32,000 to 41,000 U.S. patients—are proceeding on track.

The biotech’s gene therapy programs are in the early stages of development but includes a program for rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP)—also licensed from UPenn and UFRF—that is expected to start phase 1/2 testing in 2020. It’s also working with the University of Massachusetts Medical School on a ‘minigene’ approach to retinal diseases.

With Versant as a backer, Ophthotech is also on the lookout for additional pipeline-boosting deals, said Sblendorio, and acquiring Inception 4 has added around $6 million to the biotech’s cash pot, which stood at around $135 million at the end of the third quarter.