Adverum Biotechnologies Gains Momentum in Gene Therapy



CHICAGO—Adverum is a gene therapy company “committed to discovering and developing novel medicines that can offer life-changing benefits to patients living with rare diseases or disease of the eye who currently have limited or burdensome treatment options.” With a cash balance of $241 million, 29 issued patents, and another 90 applications pending globally, Adverum has already forged strategic relationships with Regeneron and Editas, Paul Cleveland, CEO, said here during the Ophthalmology Innovation Summit.

The company’s lead program pipeline includes three gene therapies in preclinical development – for wet age-related macular degeneration, for A1AT deficiency, and for hereditary angioedema. Regeneron has partnered with the company to develop AVA-311 for ocular disease and an additional three targets for undisclosed indications, Cleveland said. Editas is working with Adverum to develop up to five undisclosed targets for the treatment of inherited retinal disease.

The company’s AAN-001 (for A1AT deficiency) and AAN-002 (for hereditary angioedema) “hold the promise of long-term continuous expression of anti-VEGF protein with a single administration,” Cleveland stated. With “real-world data indicating a de facto ‘undertreatment’ and suboptimal visual outcomes for patients,” gene therapy may become the preferred treatment option, if confirmatory studies can replicate early preclinical outcomes. In a non-human primate model, “a single intravitreal injection of ADVM-011 or ADVM-032 demonstrated comparable efficacy to standard of care intravitreal anti-vascular endothelial growth factor protein in a laser choroidal neovascularization model,” he said. The two therapies involve novel vectors and a novel capsid, with promising preclinical results. The company expects to begin a safety and tolerability study in the first half of 2017, and will evaluate the continued durability of the anti-VEGF protein expression beyond 20 weeks, with hopes that successful outcomes will enable Adverum to file an IND.

“We’re using our in-house process development capabilities to deliver turnkey large-scale processes,” Cleveland explained. The company has a scalable upstream process to use the baculovirus/SF9 system of expression for AAV production. It will continue to improve on existing technology through its research on next-generation vectors “for better transduction efficiency and antibody neutralization profiles,” and will work on discovery of improved ubiquitous and cell-specific promoters and expression cassettes for optimal transgene expression upon transduction in target tissue, he added.

The company’s existing cash “is expected to be enough to fund our lead programs through meaningful human proof-of-concept studies,” Cleveland said.

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