Vertex-Affinia partnership: expanding the gene therapy toolkit

Allie Nawrat 7 May 2020 (Last Updated May 6th, 2020 15:46)

Building on the success of its gene-targeted cystic fibrosis therapies, Vertex has begun to expand into new disease areas that would benefit from a similar gene therapy approach. To this end, it has begun to develop a toolkit of technology to support drug development in new spaces, including DMD and DM1, bringing on-board AAV capsid-focused Affinia.

Vertex-Affinia partnership: expanding the gene therapy toolkit
Vertex’s campus in Boston, US. Credit: Shutterstock.

At the end of April, Vertex Pharmaceuticals and Affinia Therapeutics initiated a strategic research collaboration. Under the terms of the agreement, Affinia’s novel adeno-associated virus (AAV) capsid engineering expertise will be leveraged to develop gene therapies for Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1) and cystic fibrosis (CF).

Affinia has created the proprietary AAVSmartLibrary, as well as associated technology, to create improved capsids, which are viral protein shells. AAV capsids are seen as a particularly promising delivery method for in vivo gene therapies, since AAVs are non-pathogenic and cannot be integrated into the genome of target cells, as explained by Harvard University’s Wyss Institute.

According to the terms of the collaboration, Affinia will take responsibility for the discovery of the capsids, while Vertex will oversee the design and manufacturing of the gene therapies that incorporate these capsids, as well as clinical development and commercialisation.

This agreement gives Vertex an exclusive license to Affinia’s proprietary technology and intellectual property in DMD and DM1, as well as a right to license rights for CF and another undisclosed condition.

Affinia will be eligible for over $1.6bn in upfront payments and development, regulatory and commercial milestones – $80m of which can be paid by Vertex during the research agreement’s term.

Why Affinia Therapeutics? 

“We performed a thorough landscape search for AAV technologies that could provide novel capsids with exceptional properties for the development of genetic therapies in multiple disease areas,” explains Vertex spokesperson Heather Nichols. “Affinia’s technology platform was very attractive because the libraries are designed rationally, resulting in a highly bioactive library that can be used as a starting point to optimise capsids with desired therapeutic profiles.”

In addition, Nichols notes the scientific expertise that underlies Affinia’s work. Its technology was licensed from Lonza and Massachusetts Eye and Ear, and then further developed by Dr Luk Vandenberghe, “a world-leading AAV expert” who is a scientific co-founder of the company.  Nicholls concludes: “Together, the innovative technology and outstanding people made Affinia the clear choice for our partnership.”

Affinia CEO Rick Modi stated: “We are thankful for the scientific validation this partnership brings and look forward to working closely with [Vertex] to advance life-changing, differentiated genetic therapies and make a meaningful difference to those affected by these diseases.”

The small company’s promise is also clear from its closing of an oversubscribed $60m Series A financing round in March 2020. This funding was co-led by F-Prime Capital and New Enterprise Associates (NEA), and supported by Atlas Venture, Alexandria Venture Investments, Partners Innovation Fund and Lonza.

NEA general partner Ed Mather noted: “Affinia Therapeutics’ methodical process for designing and evaluating vectors is a differentiated approach to gene therapy, and the highly experienced leadership team will help carry these discoveries to the development, manufacturing and commercialisation of transformative medicines.”

Becoming part of Vertex’s toolkit

This deal builds on Vertex’s strong history in treating the genetic, underlying causes of serious diseases. The company has been a major player in the CF field since its founding over three decades ago; it currently has four drugs approved that target the underlying genetic basis of CF.

However, over the past few years, Vertex has committed to expanding its expertise to treating other serious diseases caused by genetic mutations or defects. It has been committed to building a “toolkit of technologies and capabilities that will allow us to pursue the diseases we’re interested in from all angles – including genetic therapies,” Nichols adds.

“Affinia Therapeutics’ innovative approach to the discovery and design of AAV capsids brings yet another tool to our Vertex Cell and Genetic Therapies toolkit, and we’re excited to partner with them to bring together their technology platform with our research and development expertise,” said Vertex executive vice-president and chief of cell and gene therapies Bastiano Sanna.

Other members of Vertex’s tool kit focusing on the DMD and DM1 field specifically include CRISPR Therapeutics and Exonics Therapeutics.

In June last year, Vertex expanded an existing four-year collaboration with CRISPR to develop new treatments for genetic causes of human diseases. The initial focus of the agreement was transfusion-dependent beta thalassemia and sickle cell disease; in November, the partners announced positive interim data from their investigational therapy CTX001 in Phase I/II studies in these two patient groups.

“Through the expanded collaboration with CRISPR and the acquisition of Exonics, we are bringing together the intellectual property, technologies, and scientific expertise needed to establish a leading gene editing platform for DMD and DM1,” stated Vertex CEO, chairman and president Jeffrey Leiden.

Other therapeutic areas also on Vertex’s gene-focused radar are type 1 diabetes through a deal with Semma signed in September last year.

Impact on Vertex’s share price

Vertex is headquartered in Boston, Massachusetts, and is listed on the New York Stock Exchange.