Pfizer inks deal with Voyager on AAV capsids for gene therapy

Pfizer entered into an agreement, potentially worth more than $600 million, to gain access to adeno-associated virus (AAV) capsids derived from Voyager Therapeutics' RNA-driven TRACER screening technology. Seng Cheng, chief scientific officer of Pfizer's rare disease research unit, said Wednesday that the company would be looking to use these additional capsids to develop gene therapies for neurologic and cardiovascular diseases, noting "we are impressed with Voyager's results to date."

According to Voyager, AAV capsids derived from its platform have shown enhanced cardiac muscle tropism and the ability to penetrate the blood-brain barrier. The drugmaker noted that its capsids also allow for better transgene expression in target tissues, citing preclinical data for one capsid candidate that demonstrated more than 1000-fold increased transgene expression in the brain compared to conventional AAV9. It said another capsid candidate showed "significantly enhanced" cardiac muscle transduction and dorsal root ganglia de-targeting versus conventional AAV9.

Safer gene therapies?  

Michael Higgins, who has held the role of interim CEO at Voyager since Andre Turenne stepped down in June, said the transaction with Pfizer "highlights the potential of our TRACER platform to identify novel AAV capsids that target desired cells and tissues with greater specificity at lower doses and with fewer off-target risks than conventional AAV serotypes."

The deal gives Pfizer the right to evaluate capsids selected for central nervous system and cardiac tropisms from the TRACER platform. Pfizer will be able to option capsids for exclusive use in developing AAV gene therapies, incorporating two undisclosed transgenes that are distinct from those planned for Voyager's own internal pipeline. Pfizer will pay Voyager $30 million upfront, as well as up to $20 million in exercise fees for two options and up to $580 million in milestones. Voyager also stands to receive mid- to high-single-digit tiered sales royalties.

Some good news following setbacks

The deal marks a bright spot for Voyager following a series of setbacks for the company over the last few years. A clinical trial for its Huntington's disease gene therapy VY-HTT01 was hit with an FDA clinical hold last year over chemistry, manufacturing and controls matters, although that has since been lifted. Meanwhile, its partner Neurocrine Biosciences pulled out of a collaboration on the VY-AADC gene therapy programme for Parkinson's disease in August following another FDA hold. AbbVie also bailed on its tau and alpha-synuclein vectorised antibody collaborations with Voyager last year.

Meanwhile, the gene therapy sector as a whole has seen a number of safety issues hobble development efforts. A few weeks ago, Pfizer was forced to amend the study protocol for a trial of its gene therapy fordadistrogene movaparvovec in Duchenne muscular dystrophy after reports of muscle weakness (see ViewPoints: Pfizer discloses latest DMD gene therapy bobble). Astellas also recently disclosed the death of a fourth patient in a study of its experimental gene therapy AT132 for patients with X-linked myotubular myopathy, while BioMarin Pharmaceutical has had to put a phenylketonuria trial of its gene therapy BMN 307 on hold as well because of liver tumours seen in preclinical testing.

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